Abstract
Cholesterol is a key molecule for synaptic transmission, and both central and peripheral synapses are cholesterol rich. During intense neuronal activity, a substantial portion of synaptic cholesterol can be oxidized by either enzymatic or non-enzymatic pathways to form oxysterols, which in turn modulate the activities of neurotransmitter receptors (e.g., NMDA and adrenergic receptors), signaling molecules (nitric oxide synthases, protein kinase C, liver X receptors), and synaptic vesicle cycling involved in neurotransmitters release. 24-Hydroxycholesterol, produced by neurons in the brain, could directly affect neighboring synapses and change neurotransmission. 27-Hydroxycholesterol, which can cross the blood–brain barrier, can alter both synaptogenesis and synaptic plasticity. Increased generation of 25-hydroxycholesterol by activated microglia and macrophages could link inflammatory processes to learning and neuronal regulation. Amyloids and oxidative stress can lead to an increase in the levels of ring-oxidized sterols and some of these oxysterols (4-cholesten-3-one, 5α-cholestan-3-one, 7β-hydroxycholesterol, 7-ketocholesterol) have a high potency to disturb or modulate neurotransmission at both the presynaptic and postsynaptic levels. Overall, oxysterols could be used as “molecular prototypes” for therapeutic approaches. Analogs of 24-hydroxycholesterol (SGE-301, SGE-550, SAGE718) can be used for correction of NMDA receptor hypofunction-related states, whereas inhibitors of cholesterol 24-hydroxylase, cholestane-3β,5α,6β-triol, and cholest-4-en-3-one oxime (olesoxime) can be utilized as potential anti-epileptic drugs and (or) protectors from excitotoxicity.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- 7β-HC:
-
7β-Hydroxycholesterol
- 7-KC:
-
7-Ketocholesterol
- 24-HC:
-
24-Hydroxycholesterol
- 27-HC:
-
27-Hydroxycholesterol
- ALS:
-
Amyotrophic lateral sclerosis
- AMPA receptor:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- CNS:
-
Central nerve system
- CSF:
-
Cerebrospinal fluid
- ER:
-
Endoplasmic reticulum
- GABA:
-
Gamma aminobutyric acid
- LTP:
-
Long-term potentiation
- LXR:
-
Liver X receptor
- NMDA receptor:
-
N-Methyl-d-aspartate receptor
- NMJ:
-
Neuromuscular junction
- NO:
-
Nitric oxide
- ROS:
-
Reactive oxygen species
- VDAC:
-
Voltage-dependent anion channel
References
Abdel-Khalik J, Yutuc E, Crick PJ, Gustafsson JA, Warner M, Roman G, Talbot K, Gray E, Griffiths WJ, Turner MR, Wang Y (2017) Defective cholesterol metabolism in amyotrophic lateral sclerosis. J Lipid Res 58(1):267–278. https://doi.org/10.1194/jlr.P071639
Akaaboune M, Allinquant B, Farza H, Roy K, Magoul R, Fiszman M, Festoff BW, Hantai D (2000) Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle. Mol Cell Neurosci 15(4):355–367. https://doi.org/10.1006/mcne.2000.0834
Ali T, Hannaoui S, Nemani S, Tahir W, Zemlyankina I, Cherry P, Shim SY, Sim V, Schaetzl HM, Gilch S (2021) Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice. Acta Neuropathol Commun 9(1):58. https://doi.org/10.1186/s40478-021-01162-1
Andersson S, Gustafsson N, Warner M, Gustafsson JA (2005) Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice. Proc Natl Acad Sci U S A 102(10):3857–3862. https://doi.org/10.1073/pnas.0500634102
Archer A, Laurencikiene J, Ahmed O, Steffensen KR, Parini P, Gustafsson JA, Korach-Andre M (2014) Skeletal muscle as a target of LXR agonist after long-term treatment: focus on lipid homeostasis. Am J Physiol Endocrinol Metab 306(5):E494–E502. https://doi.org/10.1152/ajpendo.00410.2013
Arundine M, Tymianski M (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34(4–5):325–337. https://doi.org/10.1016/s0143-4160(03)00141-6
Ball JB, Green-Fulgham SM, Watkins LR (2022) Mechanisms of microglia-mediated synapse turnover and synaptogenesis. Prog Neurobiol 218:102336. https://doi.org/10.1016/j.pneurobio.2022.102336
Bardsley EN, Paterson DJ (2020) Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches. J Physiol 598(14):2957–2976. https://doi.org/10.1113/JP276962
Bednarska K, Kielbik M, Sulowska Z, Dziadek J, Klink M (2014) Cholesterol oxidase binds TLR2 and modulates functional responses of human macrophages. Mediators Inflamm 2014:498395. https://doi.org/10.1155/2014/498395
Belotti E, Schaeffer L (2020) Regulation of gene expression at the neuromuscular junction. Neurosci Lett 735:135163. https://doi.org/10.1016/j.neulet.2020.135163
Bhogal NK, Hasan A, Gorelik J (2018) The development of compartmentation of cAMP signaling in cardiomyocytes: the role of T-tubules and caveolae microdomains. J Cardiovasc Dev Dis 5(2). https://doi.org/10.3390/jcdd5020025
Bigini P, Steffensen KR, Ferrario A, Diomede L, Ferrara G, Barbera S, Salzano S, Fumagalli E, Ghezzi P, Mennini T, Gustafsson JA (2010) Neuropathologic and biochemical changes during disease progression in liver X receptor beta-/- mice, a model of adult neuron disease. J Neuropathol Exp Neurol 69(6):593–605. https://doi.org/10.1097/NEN.0b013e3181df20e1
Binotti B, Jahn R, Perez-Lara A (2021) An overview of the synaptic vesicle lipid composition. Arch Biochem Biophys 709:108966. https://doi.org/10.1016/j.abb.2021.108966
Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J (1998) Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 39(8):1594–1600
Bordet T, Buisson B, Michaud M, Drouot C, Galea P, Delaage P, Akentieva NP, Evers AS, Covey DF, Ostuni MA, Lacapere JJ, Massaad C, Schumacher M, Steidl EM, Maux D, Delaage M, Henderson CE, Pruss RM (2007) Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 322(2):709–720. https://doi.org/10.1124/jpet.107.123000
Bordet T, Buisson B, Michaud M, Abitbol JL, Marchand F, Grist J, Andriambeloson E, Malcangio M, Pruss RM (2008) Specific antinociceptive activity of cholest-4-en-3-one, oxime (TRO19622) in experimental models of painful diabetic and chemotherapy-induced neuropathy. J Pharmacol Exp Ther 326(2):623–632. https://doi.org/10.1124/jpet.108.139410
Brachet A, Norwood S, Brouwers JF, Palomer E, Helms JB, Dotti CG, Esteban JA (2015) LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery. J Cell Biol 208(6):791–806. https://doi.org/10.1083/jcb.201407122
Brooks SW, Dykes AC, Schreurs BG (2017) A high-cholesterol diet increases 27-hydroxycholesterol and modifies estrogen receptor expression and neurodegeneration in rabbit hippocampus. J Alzheimers Dis 56(1):185–196. https://doi.org/10.3233/JAD-160725
Burns MP, Noble WJ, Olm V, Gaynor K, Casey E, LaFrancois J, Wang L, Duff K (2003) Co-localization of cholesterol, apolipoprotein E and fibrillar Abeta in amyloid plaques. Brain Res Mol Brain Res 110(1):119–125. https://doi.org/10.1016/s0169-328x(02)00647-2
Burrinha T, Martinsson I, Gomes R, Terrasso AP, Gouras GK, Almeida CG (2021) Upregulation of APP endocytosis by neuronal aging drives amyloid-dependent synapse loss. J Cell Sci 134(9). https://doi.org/10.1242/jcs.255752
Caldwell JH, Klevanski M, Saar M, Muller UC (2013) Roles of the amyloid precursor protein family in the peripheral nervous system. Mech Dev 130(6–8):433–446. https://doi.org/10.1016/j.mod.2012.11.001
Carlson BM, Carlson JA, Dedkov EI, McLennan IS (2003) Concentration of caveolin-3 at the neuromuscular junction in young and old rat skeletal muscle fibers. J Histochem Cytochem 51(9):1113–1118. https://doi.org/10.1177/002215540305100901
Carriedo SG, Sensi SL, Yin HZ, Weiss JH (2000) AMPA exposures induce mitochondrial Ca(2+) overload and ROS generation in spinal motor neurons in vitro. J Neurosci 20(1):240–250. https://doi.org/10.1523/JNEUROSCI.20-01-00240.2000
Cartagena CM, Ahmed F, Burns MP, Pajoohesh-Ganji A, Pak DT, Faden AI, Rebeck GW (2008) Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain. J Neurotrauma 25(9):1087–1098. https://doi.org/10.1089/neu.2007.0444
Cataldi GG, Elorza SD, Toledano-Zaragoza A, de Olmos S, Cragnolini AB, Martin MG (2023) Cholesterol-24-hydroxylase (CYP46) in the old brain: Analysis of positive populations and factors triggering its expression in astrocytes. J Comp Neurol 531(3):486–499. https://doi.org/10.1002/cne.25436
Chachaj-Brekiesz A, Wnetrzak A, Wlodarska S, Lipiec E, Dynarowicz-Latka P (2020) Molecular insight into neurodegeneration—Langmuir monolayer study on the influence of oxysterols on model myelin sheath. J Steroid Biochem Mol Biol 202:105727. https://doi.org/10.1016/j.jsbmb.2020.105727
Chang JY, Liu LZ (1997) 25-Hydroxycholesterol causes death but does not prevent nerve growth factor-induced neurite outgrowth in PC12 cells. Neurochem Int 31(4):517–523. https://doi.org/10.1016/s0197-0186(97)00020-x
Chang JY, Phelan KD, Chavis JA (1998) Neurotoxicity of 25-OH-cholesterol on sympathetic neurons. Brain Res Bull 45(6):615–622. https://doi.org/10.1016/s0361-9230(97)00461-9
Chen BT, Avshalumov MV, Rice ME (2001) H(2)O(2) is a novel, endogenous modulator of synaptic dopamine release. J Neurophysiol 85(6):2468–2476. https://doi.org/10.1152/jn.2001.85.6.2468
Chen J, Zhang X, Kusumo H, Costa LG, Guizzetti M (2013) Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis. Biochim Biophys Acta 1831(2):263–275. https://doi.org/10.1016/j.bbalip.2012.09.007
Coleman MP (2022) Axon biology in ALS: mechanisms of axon degeneration and prospects for therapy. Neurotherapeutics 19(4):1133–1144. https://doi.org/10.1007/s13311-022-01297-6
Cuddy LK, Winick-Ng W, Rylett RJ (2014) Regulation of the high-affinity choline transporter activity and trafficking by its association with cholesterol-rich lipid rafts. J Neurochem 128(5):725–740. https://doi.org/10.1111/jnc.12490
Cyster JG, Dang EV, Reboldi A, Yi T (2014) 25-Hydroxycholesterols in innate and adaptive immunity. Nat Rev Immunol 14(11):731–743. https://doi.org/10.1038/nri3755
Dadsena S, Bockelmann S, Mina JGM, Hassan DG, Korneev S, Razzera G, Jahn H, Niekamp P, Muller D, Schneider M, Tafesse FG, Marrink SJ, Melo MN, Holthuis JCM (2019) Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Nat Commun 10(1):1832. https://doi.org/10.1038/s41467-019-09654-4
D’Alonzo ZJ, Lam V, Takechi R, Nesbit M, Vaccarezza M, Mamo JCL (2023) Peripheral metabolism of lipoprotein-amyloid beta as a risk factor for Alzheimer’s disease: potential interactive effects of APOE genotype with dietary fats. Genes Nutr 18(1):2. https://doi.org/10.1186/s12263-023-00722-5
Darbandi-Tonkabon R, Manion BD, Hastings WR, Craigen WJ, Akk G, Bracamontes JR, He Y, Sheiko TV, Steinbach JH, Mennerick SJ, Covey DF, Evers AS (2004) Neuroactive steroid interactions with voltage-dependent anion channels: lack of relationship to GABA(A) receptor modulation and anesthesia. J Pharmacol Exp Ther 308(2):502–511. https://doi.org/10.1124/jpet.103.058123
DeBarber AE, Sandlers Y, Pappu AS, Merkens LS, Duell PB, Lear SR, Erickson SK, Steiner RD (2011) Profiling sterols in cerebrotendinous xanthomatosis: Utility of Girard derivatization and high resolution exact mass LC-ESI-MSn analysis. J Chromatogr B 879(17-18):1384–1392. https://doi.org/10.1016/j.jchromb.2010.11.019
Deckert V, Persegol L, Viens L, Lizard G, Athias A, Lallemant C, Gambert P, Lagrost L (1997) Inhibitors of arterial relaxation among components of human oxidized low-density lipoproteins. Cholesterol derivatives oxidized in position 7 are potent inhibitors of endothelium-dependent relaxation. Circulation 95(3):723–731. https://doi.org/10.1161/01.cir.95.3.723
Deckert V, Duverneuil L, Poupon S, Monier S, Le Guern N, Lizard G, Masson D, Lagrost L (2002) The impairment of endothelium-dependent arterial relaxation by 7-ketocholesterol is associated with an early activation of protein kinase C. Br J Pharmacol 137(5):655–662. https://doi.org/10.1038/sj.bjp.0704920
Delgado T, Petralia RS, Freeman DW, Sedlacek M, Wang YX, Brenowitz SD, Sheu SH, Gu JW, Kapogiannis D, Mattson MP, Yao PJ (2019) Comparing 3D ultrastructure of presynaptic and postsynaptic mitochondria. Biol Open 8(8). https://doi.org/10.1242/bio.044834
Denker A, Krohnert K, Buckers J, Neher E, Rizzoli SO (2011) The reserve pool of synaptic vesicles acts as a buffer for proteins involved in synaptic vesicle recycling. Proc Natl Acad Sci U S A 108(41):17183–17188. https://doi.org/10.1073/pnas.1112690108
Di Natale MR, Stebbing MJ, Furness JB (2021) Autonomic neuromuscular junctions. Auton Neurosci 234:102816. https://doi.org/10.1016/j.autneu.2021.102816
Di Natale C, Monaco A, Pedone C, Trojsi F, Tedeschi G, Netti PA, Abrescia P (2023) Levels of 24-hydroxycholesteryl esters in cerebrospinal fluid and plasma from patients with amyotrophic lateral sclerosis. J Pharm Biomed Anal 226:115244. https://doi.org/10.1016/j.jpba.2023.115244
Dissing-Olesen L, LeDue JM, Rungta RL, Hefendehl JK, Choi HB, MacVicar BA (2014) Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J Neurosci 34(32):10511–10527. https://doi.org/10.1523/JNEUROSCI.0405-14.2014
Dodge JC, Yu J, Sardi SP, Shihabuddin LS (2021) Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis. Sci Rep 11(1):803. https://doi.org/10.1038/s41598-020-80378-y
Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR (2003) Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry 42(10):2768–2773. https://doi.org/10.1021/bi0272151
Duplan L, Bernard N, Casseron W, Dudley K, Thouvenot E, Honnorat J, Rogemond V, De Bovis B, Aebischer P, Marin P, Raoul C, Henderson CE, Pettmann B (2010) Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death. J Neurosci 30(2):785–796. https://doi.org/10.1523/JNEUROSCI.5411-09.2010
d’Uscio LV, He T, Katusic ZS (2017) Expression and processing of amyloid precursor protein in vascular endothelium. Physiology (Bethesda) 32(1):20–32. https://doi.org/10.1152/physiol.00021.2016
Eckert GP, Eckert SH, Eckmann J, Hagl S, Muller WE, Friedland K (2020) Olesoxime improves cerebral mitochondrial dysfunction and enhances Abeta levels in preclinical models of Alzheimer’s disease. Exp Neurol 329:113286. https://doi.org/10.1016/j.expneurol.2020.113286
Eckmann J, Clemens LE, Eckert SH, Hagl S, Yu-Taeger L, Bordet T, Pruss RM, Muller WE, Leuner K, Nguyen HP, Eckert GP (2014) Mitochondrial membrane fluidity is consistently increased in different models of Huntington disease: restorative effects of olesoxime. Mol Neurobiol 50(1):107–118. https://doi.org/10.1007/s12035-014-8663-3
Elia J, Carbonnelle D, Loge C, Ory L, Huvelin JM, Tannoury M, Diab-Assaf M, Petit K, Nazih H (2019) 4-cholesten-3-one decreases breast cancer cell viability and alters membrane raft-localized EGFR expression by reducing lipogenesis and enhancing LXR-dependent cholesterol transporters. Lipids Health Dis 18(1):168. https://doi.org/10.1186/s12944-019-1103-7
Elliott-Hunt CR, Pope RJ, Vanderplank P, Wynick D (2007) Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage. J Neurochem 100(3):780–789. https://doi.org/10.1111/j.1471-4159.2006.04239.x
Fabiani C, Georgiev VN, Penalva DA, Sigaut L, Pietrasanta L, Corradi J, Dimova R, Antollini SS (2022) Membrane lipid organization and nicotinic acetylcholine receptor function: A two-way physiological relationship. Arch Biochem Biophys 730:109413. https://doi.org/10.1016/j.abb.2022.109413
Faria-Pereira A, Morais VA (2022) Synapses: the brain’s energy-demanding sites. Int J Mol Sci 23(7). https://doi.org/10.3390/ijms23073627
Franzoso M, Zaglia T, Mongillo M (2016) Putting together the clues of the everlasting neuro-cardiac liaison. Biochim Biophys Acta 1863(7 Pt B):1904–1915. https://doi.org/10.1016/j.bbamcr.2016.01.009
Gafurova CR, Tsentsevitsky AN, Petrov AM (2022) Frequency-dependent engagement of synaptic vesicle pools in the mice motor nerve terminals. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-022-01202-x
Garcia-Cardena G, Martasek P, Masters BS, Skidd PM, Couet J, Li S, Lisanti MP, Sessa WC (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem 272(41):25437–25440. https://doi.org/10.1074/jbc.272.41.25437
Geoffroy C, Paoletti P, Mony L (2022) Positive allosteric modulation of NMDA receptors: mechanisms, physiological impact and therapeutic potential. J Physiol 600(2):233–259. https://doi.org/10.1113/JP280875
Giménez y Ribotta M, Rajaofetra N, Morin-Richaud C, Alonso G, Bochelen D, Sandillon F, Legrand A, Mersel M, Privat A (1995) Oxystdrol (7β-hydroxycholestesteryl-3-oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction. J Neurosci Res 41(1):79–95. https://doi.org/10.1002/jnr.490410110
Giniatullin A, Petrov A, Giniatullin R (2015) The involvement of P2Y12 receptors, NADPH oxidase, and lipid rafts in the action of extracellular ATP on synaptic transmission at the frog neuromuscular junction. Neuroscience 285:324–332. https://doi.org/10.1016/j.neuroscience.2014.11.039
Graykowski DR, Wang YZ, Upadhyay A, Savas JN (2020) The dichotomous role of extracellular vesicles in the central nervous system. iScience 23(9):101456. https://doi.org/10.1016/j.isci.2020.101456
Griguoli M, Sgritta M, Cherubini E (2016) Presynaptic BK channels control transmitter release: physiological relevance and potential therapeutic implications. J Physiol 594(13):3489–3500. https://doi.org/10.1113/JP271841
Gu X, Li A, Liu S, Lin L, Xu S, Zhang P, Li S, Li X, Tian B, Zhu X, Wang X (2016) MicroRNA124 regulated neurite elongation by targeting OSBP. Mol Neurobiol 53(9):6388–6396. https://doi.org/10.1007/s12035-015-9540-4
Guedes JR, Ferreira PA, Costa JM, Cardoso AL, Peca J (2022) Microglia-dependent remodeling of neuronal circuits. J Neurochem 163(2):74–93. https://doi.org/10.1111/jnc.15689
Gundelfinger ED, Karpova A, Pielot R, Garner CC, Kreutz MR (2022) Organization of presynaptic autophagy-related processes. Front Synaptic Neurosci 14:829354. https://doi.org/10.3389/fnsyn.2022.829354
Hahn CD, Jiang Y, Villanueva V, Zolnowska M, Arkilo D, Hsiao S, Asgharnejad M, Dlugos D (2022) A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (ELEKTRA). Epilepsia 63(10):2671–2683. https://doi.org/10.1111/epi.17367
Han JH, Kim YJ, Han ES, Lee CS (2007) Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by calmodulin inhibition. Brain Res 1137(1):11–19. https://doi.org/10.1016/j.brainres.2006.12.041
Han M, Wang S, Yang N, Wang X, Zhao W, Saed HS, Daubon T, Huang B, Chen A, Li G, Miletic H, Thorsen F, Bjerkvig R, Li X, Wang J (2020) Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma. EMBO Mol Med 12(1):e10924. https://doi.org/10.15252/emmm.201910924
Hawkins NA, Jurado M, Thaxton TT, Duarte SE, Barse L, Tatsukawa T, Yamakawa K, Nishi T, Kondo S, Miyamoto M, Abrahams BS, During MJ, Kearney JA (2021) Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice. Epilepsia 62(11):2845–2857. https://doi.org/10.1111/epi.17062
He X, Jenner AM, Ong WY, Farooqui AA, Patel SC (2006) Lovastatin modulates increased cholesterol and oxysterol levels and has a neuroprotective effect on rat hippocampal neurons after kainate injury. J Neuropathol Exp Neurol 65(7):652–663. https://doi.org/10.1097/01.jnen.0000225906.82428.69
Head BP, Patel HH, Tsutsumi YM, Hu Y, Mejia T, Mora RC, Insel PA, Roth DM, Drummond JC, Patel PM (2008) Caveolin-1 expression is essential for N-methyl-D-aspartate receptor-mediated Src and extracellular signal-regulated kinase 1/2 activation and protection of primary neurons from ischemic cell death. FASEB J 22(3):828–840. https://doi.org/10.1096/fj.07-9299com
Henriksson J (1991) Effect of exercise on amino acid concentrations in skeletal muscle and plasma. J Exp Biol 160:149–165. https://doi.org/10.1242/jeb.160.1.149
Henson MA, Tucker CJ, Zhao M, Dudek SM (2017) Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning. Neurobiol Learn Mem 138:39–53. https://doi.org/10.1016/j.nlm.2016.10.013
Heverin M, Meaney S, Lutjohann D, Diczfalusy U, Wahren J, Bjorkhem I (2005) Crossing the barrier: net flux of 27-hydroxycholesterol into the human brain. J Lipid Res 46(5):1047–1052. https://doi.org/10.1194/jlr.M500024-JLR200
Hezel M, de Groat WC, Galbiati F (2010) Caveolin-3 promotes nicotinic acetylcholine receptor clustering and regulates neuromuscular junction activity. Mol Biol Cell 21(2):302–310. https://doi.org/10.1091/mbc.e09-05-0381
Hichor M, Sundaram VK, Eid SA, Abdel-Rassoul R, Petit PX, Borderie D, Bastin J, Eid AA, Manuel M, Grenier J, Massaad C (2018) Liver X Receptor exerts a protective effect against the oxidative stress in the peripheral nerve. Sci Rep 8(1):2524. https://doi.org/10.1038/s41598-018-20980-3
Hill MD, Blanco MJ, Salituro FG, Bai Z, Beckley JT, Ackley MA, Dai J, Doherty JJ, Harrison BL, Hoffmann EC, Kazdoba TM, Lanzetta D, Lewis M, Quirk MC, Robichaud AJ (2022) SAGE-718: a first-in-class N-methyl-d-aspartate receptor positive allosteric modulator for the potential treatment of cognitive impairment. J Med Chem 65(13):9063–9075. https://doi.org/10.1021/acs.jmedchem.2c00313
Hu H, Zhou Y, Leng T, Liu A, Wang Y, You X, Chen J, Tang L, Chen W, Qiu P, Yin W, Huang Y, Zhang J, Wang L, Sang H, Yan G (2014) The major cholesterol metabolite cholestane-3beta,5alpha,6beta-triol functions as an endogenous neuroprotectant. J Neurosci 34(34):11426–11438. https://doi.org/10.1523/JNEUROSCI.0344-14.2014
Hudry E, Van Dam D, Kulik W, De Deyn PP, Stet FS, Ahouansou O, Benraiss A, Delacourte A, Bougneres P, Aubourg P, Cartier N (2010) Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer’s disease. Mol Ther 18(1):44–53. https://doi.org/10.1038/mt.2009.175
Ishikawa T, Yuhanna IS, Umetani J, Lee WR, Korach KS, Shaul PW, Umetani M (2013) LXRbeta/estrogen receptor-alpha signaling in lipid rafts preserves endothelial integrity. J Clin Invest 123(8):3488–3497. https://doi.org/10.1172/JCI66533
Ishikawa M, Yoshitomi T, Zorumski CF, Izumi Y (2014) Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model. Invest Ophthalmol Vis Sci 55(12):8531–8541. https://doi.org/10.1167/iovs.14-15624
Ishikawa M, Yoshitomi T, Zorumski CF, Izumi Y (2016) 24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure. Sci Rep 6:33886. https://doi.org/10.1038/srep33886
Ishikawa M, Yoshitomi T, Covey DF, Zorumski CF, Izumi Y (2018) Additive neuroprotective effects of 24(S)-hydroxycholesterol and allopregnanolone in an ex vivo rat glaucoma model. Sci Rep 8(1):12851. https://doi.org/10.1038/s41598-018-31239-2
Ismail MA, Mateos L, Maioli S, Merino-Serrais P, Ali Z, Lodeiro M, Westman E, Leitersdorf E, Gulyas B, Olof-Wahlund L, Winblad B, Savitcheva I, Bjorkhem I, Cedazo-Minguez A (2017) 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation. J Exp Med 214(3):699–717. https://doi.org/10.1084/jem.20160534
Izumi Y, Mennerick SJ, Doherty JJ, Zorumski CF (2021a) Oxysterols modulate the acute effects of ethanol on hippocampal N-methyl-d-aspartate receptors, long-term potentiation, and learning. J Pharmacol Exp Ther 377(1):181–188. https://doi.org/10.1124/jpet.120.000376
Izumi Y, Cashikar AG, Krishnan K, Paul SM, Covey DF, Mennerick SJ, Zorumski CF (2021b) A proinflammatory stimulus disrupts hippocampal plasticity and learning via microglial activation and 25-hydroxycholesterol. J Neurosci 41(49):10054–10064. https://doi.org/10.1523/JNEUROSCI.1502-21.2021
Jafurulla M, Nalli A, Chattopadhyay A (2017) Membrane cholesterol oxidation in live cells enhances the function of serotonin(1A) receptors. Chem Phys Lipids 203:71–77. https://doi.org/10.1016/j.chemphyslip.2017.01.005
Jamadagni P, Patten SA (2019) 25-hydroxycholesterol impairs neuronal and muscular development in zebrafish. Neurotoxicology 75:14–23. https://doi.org/10.1016/j.neuro.2019.08.007
Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ (1999) Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci U S A 96(1):266–271. https://doi.org/10.1073/pnas.96.1.266
Jurek B, Neumann ID (2018) The oxytocin receptor: from intracellular signaling to behavior. Physiol Rev 98(3):1805–1908. https://doi.org/10.1152/physrev.00031.2017
Justs KA, Lu Z, Chouhan AK, Borycz JA, Lu Z, Meinertzhagen IA, Macleod GT (2022) Presynaptic mitochondrial volume and packing density scale with presynaptic power demand. J Neurosci 42(6):954–967. https://doi.org/10.1523/JNEUROSCI.1236-21.2021
Kacher R, Lamaziere A, Heck N, Kappes V, Mounier C, Despres G, Dembitskaya Y, Perrin E, Christaller W, Sasidharan Nair S, Messent V, Cartier N, Vanhoutte P, Venance L, Saudou F, Neri C, Caboche J, Betuing S (2019) CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington’s disease. Brain 142(8):2432–2450. https://doi.org/10.1093/brain/awz174
Kasimov MR, Giniatullin AR, Zefirov AL, Petrov AM (2015) Effects of 5alpha-cholestan-3-one on the synaptic vesicle cycle at the mouse neuromuscular junction. Biochim Biophys Acta 1851(5):674–685. https://doi.org/10.1016/j.bbalip.2015.02.012
Kasimov MR, Zakyrjanova GF, Giniatullin AR, Zefirov AL, Petrov AM (2016) Similar oxysterols may lead to opposite effects on synaptic transmission: Olesoxime versus 5alpha-cholestan-3-one at the frog neuromuscular junction. Biochim Biophys Acta 1861(7):606–616. https://doi.org/10.1016/j.bbalip.2016.04.010
Kasimov MR, Fatkhrakhmanova MR, Mukhutdinova KA, Petrov AM (2017) 24S-Hydroxycholesterol enhances synaptic vesicle cycling in the mouse neuromuscular junction: Implication of glutamate NMDA receptors and nitric oxide. Neuropharmacology 117:61–73. https://doi.org/10.1016/j.neuropharm.2017.01.030
Khan S (2022) Endoplasmic reticulum in metaplasticity: from information processing to synaptic proteostasis. Mol Neurobiol 59(9):5630–5655. https://doi.org/10.1007/s12035-022-02916-1
Kim YJ, Han JH, Han ES, Lee CS (2006) 7-Ketocholesterol enhances 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells. J Neural Transm (Vienna) 113(12):1877–1885. https://doi.org/10.1007/s00702-006-0486-6
Kim SM, Noh MY, Kim H, Cheon SY, Lee KM, Lee J, Cha E, Park KS, Lee KW, Sung JJ, Kim SH (2017) 25-Hydroxycholesterol is involved in the pathogenesis of amyotrophic lateral sclerosis. Oncotarget 8(7):11855–11867. https://doi.org/10.18632/oncotarget.14416
Kim D, Lee KM, Lee C, Jo YS, Muradillaevna MS, Kim JH, Yoon JH, Song P (2022) Pathophysiological role of 27-hydroxycholesterol in human diseases. Adv Biol Regul 83:100837. https://doi.org/10.1016/j.jbior.2021.100837
Koma H, Yamamoto Y, Okamura N, Yagami T (2020) A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-Delta(12,14)-prostaglandin J(2). Brain Behav 10(12):e01866. https://doi.org/10.1002/brb3.1866
Korinek M, Vyklicky V, Borovska J, Lichnerova K, Kaniakova M, Krausova B, Krusek J, Balik A, Smejkalova T, Horak M, Vyklicky L (2015) Cholesterol modulates open probability and desensitization of NMDA receptors. J Physiol 593(10):2279–2293. https://doi.org/10.1113/jphysiol.2014.288209
Kotti TJ, Ramirez DM, Pfeiffer BE, Huber KM, Russell DW (2006) Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci U S A 103(10):3869–3874. https://doi.org/10.1073/pnas.0600316103
Kotti T, Head DD, McKenna CE, Russell DW (2008) Biphasic requirement for geranylgeraniol in hippocampal long-term potentiation. Proc Natl Acad Sci U S A 105(32):11394–11399. https://doi.org/10.1073/pnas.0805556105
Kravtsova VV, Petrov AM, Vasil’ev AN, Zefirov AL, Krivoi II (2015) Role of cholesterol in the maintenance of endplate electrogenesis in rat diaphragm. Bull Exp Biol Med 158(3):298–300. https://doi.org/10.1007/s10517-015-2745-8
Krivoi II, Petrov AM (2019) Cholesterol and the safety factor for neuromuscular transmission. Int J Mol Sci 20(5). https://doi.org/10.3390/ijms20051046
Kuijpers M, Azarnia Tehran D, Haucke V, Soykan T (2021) The axonal endolysosomal and autophagic systems. J Neurochem 158(3):589–602. https://doi.org/10.1111/jnc.15287
Kumar R, Coggan AR, Ferreira LF (2022) Nitric oxide and skeletal muscle contractile function. Nitric Oxide 122-123:54–61. https://doi.org/10.1016/j.niox.2022.04.001
La Marca V, Maresca B, Spagnuolo MS, Cigliano L, Dal Piaz F, Di Iorio G, Abrescia P (2016) Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification? Neurosci Res 105:19–27. https://doi.org/10.1016/j.neures.2015.09.008
Lange Y, Steck TL, Ye J, Lanier MH, Molugu V, Ory D (2009) Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol. J Lipid Res 50(9):1881–1888. https://doi.org/10.1194/jlr.M900116-JLR200
Lee JH, Han JH, Woo JH, Jou I (2022) 25-Hydroxycholesterol suppress IFN-gamma-induced inflammation in microglia by disrupting lipid raft formation and caveolin-mediated signaling endosomes. Free Radic Biol Med 179:252–265. https://doi.org/10.1016/j.freeradbiomed.2021.11.017
Leoni V, Caccia C (2013) Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid. Biochem Pharmacol 86(1):26–36. https://doi.org/10.1016/j.bcp.2013.03.015
Li L, Cao D, Garber DW, Kim H, Fukuchi K (2003) Association of aortic atherosclerosis with cerebral beta-amyloidosis and learning deficits in a mouse model of Alzheimer’s disease. Am J Pathol 163(6):2155–2164. https://doi.org/10.1016/s0002-9440(10)63572-9
Limbad C, Doi R, McGirr J, Ciotlos S, Perez K, Clayton ZS, Daya R, Seals DR, Campisi J, Melov S (2022) Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types. iScience 25(2):103848. https://doi.org/10.1016/j.isci.2022.103848
Linsenbardt AJ, Taylor A, Emnett CM, Doherty JJ, Krishnan K, Covey DF, Paul SM, Zorumski CF, Mennerick S (2014) Different oxysterols have opposing actions at N-methyl-D-aspartate receptors. Neuropharmacology 85:232–242. https://doi.org/10.1016/j.neuropharm.2014.05.027
Loera-Valencia R, Vazquez-Juarez E, Munoz A, Gerenu G, Gomez-Galan M, Lindskog M, DeFelipe J, Cedazo-Minguez A, Merino-Serrais P (2021) High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus. Sci Rep 11(1):3736. https://doi.org/10.1038/s41598-021-83008-3
Loke SY, Tanaka K, Ong WY (2013) Comprehensive gene expression analyses of the rat prefrontal cortex after oxysterol treatment. J Neurochem 124(6):770–781. https://doi.org/10.1111/jnc.12142
Lorden G, Wozniak JM, Dore K, Dozier LE, Cates-Gatto C, Patrick GN, Gonzalez DJ, Roberts AJ, Tanzi RE, Newton AC (2022) Enhanced activity of Alzheimer disease-associated variant of protein kinase Calpha drives cognitive decline in a mouse model. Nat Commun 13(1):7200. https://doi.org/10.1038/s41467-022-34679-7
Loss CM, da Rosa NS, Mestriner RG, Xavier LL, Oliveira DL (2019) Blockade of GluN2B-containing NMDA receptors reduces short-term brain damage induced by early-life status epilepticus. Neurotoxicology 71:138–149. https://doi.org/10.1016/j.neuro.2019.01.002
Lu SM, Fairn GD (2018) 7-Ketocholesterol impairs phagocytosis and efferocytosis via dysregulation of phosphatidylinositol 4,5-bisphosphate. Traffic 19(8):591–604. https://doi.org/10.1111/tra.12576
Lu F, Fan S, Romo AR, Xu D, Ferriero DM, Jiang X (2020) Serum 24S-hydroxycholesterol predicts long-term brain structural and functional outcomes after hypoxia-ischemia in neonatal mice. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X20911910
Lund EG, Guileyardo JM, Russell DW (1999) cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci U S A 96(13):7238–7243. https://doi.org/10.1073/pnas.96.13.7238
Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW (2003) Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J Biol Chem 278(25):22980–22988. https://doi.org/10.1074/jbc.M303415200
Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, Bjorkhem I (1996) Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci U S A 93(18):9799–9804. https://doi.org/10.1073/pnas.93.18.9799
Ma MT, Zhang J, Farooqui AA, Chen P, Ong WY (2010) Effects of cholesterol oxidation products on exocytosis. Neurosci Lett 476(1):36–41. https://doi.org/10.1016/j.neulet.2010.03.078
Malomouzh AI, Mukhtarov MR, Nikolsky EE, Vyskocil F, Lieberman EM, Urazaev AK (2003) Glutamate regulation of non-quantal release of acetylcholine in the rat neuromuscular junction. J Neurochem 85(1):206–213. https://doi.org/10.1046/j.1471-4159.2003.01660.x
Malomouzh AI, Nurullin LF, Arkhipova SS, Nikolsky EE (2011) NMDA receptors at the endplate of rat skeletal muscles: precise postsynaptic localization. Muscle Nerve 44(6):987–989. https://doi.org/10.1002/mus.22250
Mannara F, Radosevic M, Planaguma J, Soto D, Aguilar E, Garcia-Serra A, Maudes E, Pedreno M, Paul S, Doherty J, Quirk M, Dai J, Gasull X, Lewis M, Dalmau J (2020) Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis. Brain 143(9):2709–2720. https://doi.org/10.1093/brain/awaa195
Martin MG, Pfrieger F, Dotti CG (2014) Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 15(10):1036–1052. https://doi.org/10.15252/embr.201439225
Martin-Segura A, Ahmed T, Casadome-Perales A, Palomares-Perez I, Palomer E, Kerstens A, Munck S, Balschun D, Dotti CG (2019) Age-associated cholesterol reduction triggers brain insulin resistance by facilitating ligand-independent receptor activation and pathway desensitization. Aging Cell 18(3):e12932. https://doi.org/10.1111/acel.12932
Marwarha G, Dasari B, Prasanthi JR, Schommer J, Ghribi O (2010) Leptin reduces the accumulation of Abeta and phosphorylated tau induced by 27-hydroxycholesterol in rabbit organotypic slices. J Alzheimers Dis 19(3):1007–1019. https://doi.org/10.3233/JAD-2010-1298
Mateos L, Akterin S, Gil-Bea FJ, Spulber S, Rahman A, Bjorkhem I, Schultzberg M, Flores-Morales A, Cedazo-Minguez A (2009) Activity-regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro. Brain Pathol 19(1):69–80. https://doi.org/10.1111/j.1750-3639.2008.00174.x
Mateos L, Ismail MA, Gil-Bea FJ, Leoni V, Winblad B, Bjorkhem I, Cedazo-Minguez A (2011) Upregulation of brain renin angiotensin system by 27-hydroxycholesterol in Alzheimer’s disease. J Alzheimers Dis 24(4):669–679. https://doi.org/10.3233/JAD-2011-101512
Mays TA, Sanford JL, Hanada T, Chishti AH, Rafael-Fortney JA (2009) Glutamate receptors localize postsynaptically at neuromuscular junctions in mice. Muscle Nerve 39(3):343–349. https://doi.org/10.1002/mus.21099
Meffre D, Shackleford G, Hichor M, Gorgievski V, Tzavara ET, Trousson A, Ghoumari AM, Deboux C, Nait Oumesmar B, Liere P, Schumacher M, Baulieu EE, Charbonnier F, Grenier J, Massaad C (2015) Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum. Proc Natl Acad Sci U S A 112(24):7587–7592. https://doi.org/10.1073/pnas.1424951112
Mercer AJ, Szalewski RJ, Jackman SL, Van Hook MJ, Thoreson WB (2012) Regulation of presynaptic strength by controlling Ca2+ channel mobility: effects of cholesterol depletion on release at the cone ribbon synapse. J Neurophysiol 107(12):3468–3478. https://doi.org/10.1152/jn.00779.2011
Merino-Serrais P, Loera-Valencia R, Rodriguez-Rodriguez P, Parrado-Fernandez C, Ismail MA, Maioli S, Matute E, Jimenez-Mateos EM, Bjorkhem I, DeFelipe J, Cedazo-Minguez A (2019) 27-Hydroxycholesterol induces aberrant morphology and synaptic dysfunction in hippocampal neurons. Cereb Cortex 29(1):429–446. https://doi.org/10.1093/cercor/bhy274
Micheva KD, Holz RW, Smith SJ (2001) Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity. J Cell Biol 154(2):355–368. https://doi.org/10.1083/jcb.200102098
Miguet-Alfonsi C, Prunet C, Monier S, Bessede G, Lemaire-Ewing S, Berthier A, Menetrier F, Neel D, Gambert P, Lizard G (2002) Analysis of oxidative processes and of myelin figures formation before and after the loss of mitochondrial transmembrane potential during 7beta-hydroxycholesterol and 7-ketocholesterol-induced apoptosis: comparison with various pro-apoptotic chemicals. Biochem Pharmacol 64(3):527–541. https://doi.org/10.1016/s0006-2952(02)01110-3
Miller OH, Yang L, Wang CC, Hargroder EA, Zhang Y, Delpire E, Hall BJ (2014) GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine. Elife 3:e03581. https://doi.org/10.7554/eLife.03581
Mitroi DN, Pereyra-Gomez G, Soto-Huelin B, Senovilla F, Kobayashi T, Esteban JA, Ledesma MD (2019) NPC1 enables cholesterol mobilization during long-term potentiation that can be restored in Niemann-Pick disease type C by CYP46A1 activation. EMBO Rep 20(11):e48143. https://doi.org/10.15252/embr.201948143
Mougenot N, Lesnik P, Ramirez-Gil JF, Nataf P, Diczfalusy U, Chapman MJ, Lechat P (1997) Effect of the oxidation state of LDL on the modulation of arterial vasomotor response in vitro. Atherosclerosis 133(2):183–192. https://doi.org/10.1016/s0021-9150(97)00124-x
Moutinho M, Nunes MJ, Correia JC, Gama MJ, Castro-Caldas M, Cedazo-Minguez A, Rodrigues CM, Bjorkhem I, Ruas JL, Rodrigues E (2016) Neuronal cholesterol metabolism increases dendritic outgrowth and synaptic markers via a concerted action of GGTase-I and Trk. Sci Rep 6:30928. https://doi.org/10.1038/srep30928
Mukhamedyarov MA, Khabibrakhmanov AN, Khuzakhmetova VF, Giniatullin AR, Zakirjanova GF, Zhilyakov NV, Mukhutdinova KA, Samigullin DV, Grigoryev PN, Zakharov AV, Zefirov AL, Petrov AM (2023) Early alterations in structural and functional properties in the neuromuscular junctions of mutant FUS mice. Int J Mol Sci 24(10). https://doi.org/10.3390/ijms24109022
Mukhutdinova KA, Kasimov MR, Giniatullin AR, Zakyrjanova GF, Petrov AM (2018) 24S-hydroxycholesterol suppresses neuromuscular transmission in SOD1(G93A) mice: A possible role of NO and lipid rafts. Mol Cell Neurosci 88:308–318. https://doi.org/10.1016/j.mcn.2018.03.006
Mukhutdinova KA, Kasimov MR, Zakyrjanova GF, Gumerova MR, Petrov AM (2019) Oxysterol modulates neurotransmission via liver-X receptor/NO synthase-dependent pathway at the mouse neuromuscular junctions. Neuropharmacology 150:70–79. https://doi.org/10.1016/j.neuropharm.2019.03.018
Nelson TJ, Alkon DL (2005) Oxidation of cholesterol by amyloid precursor protein and beta-amyloid peptide. J Biol Chem 280(8):7377–7387. https://doi.org/10.1074/jbc.M409071200
Nie S, Chen G, Cao X, Zhang Y (2014) Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis 9(1). https://doi.org/10.1186/s13023-014-0179-4
Nishi T, Kondo S, Miyamoto M, Watanabe S, Hasegawa S, Kondo S, Yano J, Watanabe E, Ishi T, Yoshikawa M, Ando HK, Farnaby W, Fujimoto S, Sunahara E, Ohori M, During MJ, Kuroita T, Koike T (2020) Soticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice. Sci Rep 10(1):17081. https://doi.org/10.1038/s41598-020-74036-6
Nishi T, Metcalf CS, Fujimoto S, Hasegawa S, Miyamoto M, Sunahara E, Watanabe S, Kondo S, White HS (2022) Anticonvulsive properties of soticlestat, a novel cholesterol 24-hydroxylase inhibitor. Epilepsia 63(6):1580–1590. https://doi.org/10.1111/epi.17232
Nobrega C, Mendonca L, Marcelo A, Lamaziere A, Tome S, Despres G, Matos CA, Mechmet F, Langui D, den Dunnen W, de Almeida LP, Cartier N, Alves S (2019) Restoring brain cholesterol turnover improves autophagy and has therapeutic potential in mouse models of spinocerebellar ataxia. Acta Neuropathol 138(5):837–858. https://doi.org/10.1007/s00401-019-02019-7
Noguchi N, Urano Y, Takabe W, Saito Y (2015) New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death. Free Radic Biol Med 87:366–372. https://doi.org/10.1016/j.freeradbiomed.2015.06.036
Nury T, Yammine A, Menetrier F, Zarrouk A, Vejux A, Lizard G (2020) 7-Ketocholesterol- and 7beta-hydroxycholesterol-induced peroxisomal disorders in glial, microglial and neuronal cells: potential role in neurodegeneration : 7-ketocholesterol and 7beta-hydroxycholesterol-induced peroxisomal disorders and neurodegeneration. Adv Exp Med Biol 1299:31–41. https://doi.org/10.1007/978-3-030-60204-8_3
Odnoshivkina YG, Petrov AM (2021) The role of neuro-cardiac junctions in sympathetic regulation of the heart. J Evol Biochem Physiol 57(3):527–541. https://doi.org/10.1134/s0022093021030078
Odnoshivkina UG, Petrov AM (2023) Immune oxysterol downregulates the atrial inotropic response to β-adrenergic receptor stimulation: the role of liver X receptors and lipid raft stability. J Evol Biochem Physiol 58(S1):S1–S12. https://doi.org/10.1134/s0022093022070018
Odnoshivkina YG, Sytchev VI, Petrov AM (2017) Cholesterol regulates contractility and inotropic response to beta2-adrenoceptor agonist in the mouse atria: Involvement of Gi-protein-Akt-NO-pathway. J Mol Cell Cardiol 107:27–40. https://doi.org/10.1016/j.yjmcc.2016.05.001
Odnoshivkina UG, Sytchev VI, Starostin O, Petrov AM (2019) Brain cholesterol metabolite 24-hydroxycholesterol modulates inotropic responses to beta-adrenoceptor stimulation: The role of NO and phosphodiesterase. Life Sci 220:117–126. https://doi.org/10.1016/j.lfs.2019.01.054
Odnoshivkina UG, Kuznetsova EA, Petrov AM (2022) 25-Hydroxycholesterol as a signaling molecule of the nervous system. Biochemistry (Mosc) 87(6):524–537. https://doi.org/10.1134/S0006297922060049
Odnoshivkina JG, Sibgatullina GV, Petrov AM (2023) Lipid-dependent regulation of neurotransmitter release from sympathetic nerve endings in mice atria. Biochim Biophys Acta Biomembr 1865(7):184197. https://doi.org/10.1016/j.bbamem.2023.184197
Ohyama Y, Meaney S, Heverin M, Ekstrom L, Brafman A, Shafir M, Andersson U, Olin M, Eggertsen G, Diczfalusy U, Feinstein E, Bjorkhem I (2006) Studies on the transcriptional regulation of cholesterol 24-hydroxylase (CYP46A1): marked insensitivity toward different regulatory axes. J Biol Chem 281(7):3810–3820. https://doi.org/10.1074/jbc.M505179200
Okuda K, Kobayashi S, Fukaya M, Watanabe A, Murakami T, Hagiwara M, Sato T, Ueno H, Ogonuki N, Komano-Inoue S, Manabe H, Yamaguchi M, Ogura A, Asahara H, Sakagami H, Mizuguchi M, Manabe T, Tanaka T (2017) CDKL5 controls postsynaptic localization of GluN2B-containing NMDA receptors in the hippocampus and regulates seizure susceptibility. Neurobiol Dis 106:158–170. https://doi.org/10.1016/j.nbd.2017.07.002
Oswald MC, Brooks PS, Zwart MF, Mukherjee A, West RJ, Giachello CN, Morarach K, Baines RA, Sweeney ST, Landgraf M (2018) Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila. Elife 7. https://doi.org/10.7554/eLife.39393
Ouweneel AB, Thomas MJ, Sorci-Thomas MG (2020) The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes: Thematic Review Series: Biology of Lipid Rafts. J Lipid Res 61(5):676–686. https://doi.org/10.1194/jlr.TR119000383
Pajares S, Arias A, Garcia-Villoria J, Macias-Vidal J, Ros E, de las Heras J, Giros M, Coll MJ, Ribes A (2015) Cholestane-3beta,5alpha,6beta-triol: high levels in Niemann-Pick type C, cerebrotendinous xanthomatosis, and lysosomal acid lipase deficiency. J Lipid Res 56(10):1926–1935. https://doi.org/10.1194/jlr.M060343
Pandak WM, Ren S, Marques D, Hall E, Redford K, Mallonee D, Bohdan P, Heuman D, Gil G, Hylemon P (2002) Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. J Biol Chem 277(50):48158–48164. https://doi.org/10.1074/jbc.M205244200
Pang L, Graziano M, Wang S (1999) Membrane cholesterol modulates galanin-GalR2 interaction. Biochemistry 38(37):12003–12011. https://doi.org/10.1021/bi990227a
Paul SM, Doherty JJ, Robichaud AJ, Belfort GM, Chow BY, Hammond RS, Crawford DC, Linsenbardt AJ, Shu HJ, Izumi Y, Mennerick SJ, Zorumski CF (2013) The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J Neurosci 33(44):17290–17300. https://doi.org/10.1523/JNEUROSCI.2619-13.2013
Pedersen JI, Oftebro H, Bjorkhem I (1989) Reconstitution of C27-steroid 26-hydroxylase activity from bovine brain mitochondria. Biochem Int 18(3):615–622
Personius KE, Slusher BS, Udin SB (2016) Neuromuscular NMDA receptors modulate developmental synapse elimination. J Neurosci 36(34):8783–8789. https://doi.org/10.1523/JNEUROSCI.1181-16.2016
Personius KE, Siebert D, Koch DW, Udin SB (2022) Blockage of neuromuscular glutamate receptors impairs reinnervation following nerve crush in adult mice. Front Cell Neurosci 16:1000218. https://doi.org/10.3389/fncel.2022.1000218
Petrov AM, Pikuleva IA (2019) Cholesterol 24-hydroxylation by CYP46A1: benefits of modulation for brain diseases. Neurotherapeutics 16(3):635–648. https://doi.org/10.1007/s13311-019-00731-6
Petrov AM, Kasimov MR, Giniatullin AR, Tarakanova OI, Zefirov AL (2010) The role of cholesterol in the exo- and endocytosis of synaptic vesicles in frog motor nerve endings. Neurosci Behav Physiol 40(8):894–901. https://doi.org/10.1007/s11055-010-9338-9
Petrov KA, Malomouzh AI, Kovyazina IV, Krejci E, Nikitashina AD, Proskurina SE, Zobov VV, Nikolsky EE (2013) Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N-methyl-D-aspartate receptor activation. Eur J Neurosci 37(2):181–189. https://doi.org/10.1111/ejn.12029
Petrov AM, Kasimov MR, Giniatullin AR, Zefirov AL (2014a) Effects of oxidation of membrane cholesterol on the vesicle cycle in motor nerve terminals in the frog Rana ridibunda. Neurosci Behav Physiol 44(9):1020–1030. https://doi.org/10.1007/s11055-014-0019-y
Petrov AM, Yakovleva AA, Zefirov AL (2014b) Role of membrane cholesterol in spontaneous exocytosis at frog neuromuscular synapses: reactive oxygen species-calcium interplay. J Physiol 592(22):4995–5009. https://doi.org/10.1113/jphysiol.2014.279695
Petrov AM, Zakyrjanova GF, Yakovleva AA, Zefirov AL (2015) Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion. Biochem Biophys Res Commun 456(1):145–150. https://doi.org/10.1016/j.bbrc.2014.11.049
Petrov AM, Kasimov MR, Zefirov AL (2016) Brain cholesterol metabolism and its defects: linkage to neurodegenerative diseases and synaptic dysfunction. Acta Naturae 8(1):58–73
Petrov AM, Kasimov MR, Zefirov AL (2017) Cholesterol in the pathogenesis of Alzheimer’s, Parkinson’s diseases and autism: link to synaptic dysfunction. Acta Naturae 9(1):26–37
Petrov AM, Astafev AA, Mast N, Saadane A, El-Darzi N, Pikuleva IA (2019a) The interplay between retinal pathways of cholesterol output and its effects on mouse retina. Biomolecules 9(12). https://doi.org/10.3390/biom9120867
Petrov AM, Lam M, Mast N, Moon J, Li Y, Maxfield E, Pikuleva IA (2019b) CYP46A1 activation by efavirenz leads to behavioral improvement without significant changes in amyloid plaque load in the brain of 5XFAD mice. Neurotherapeutics 16(3):710–724. https://doi.org/10.1007/s13311-019-00737-0
Petrov AM, Mast N, Li Y, Pikuleva IA (2019c) The key genes, phosphoproteins, processes, and pathways affected by efavirenz-activated CYP46A1 in the amyloid-decreasing paradigm of efavirenz treatment. FASEB J 33(8):8782–8798. https://doi.org/10.1096/fj.201900092R
Petrov AM, Mast N, Li Y, Denker J, Pikuleva IA (2020) Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes. Brain Commun 2(1). https://doi.org/10.1093/braincomms/fcaa043
Pfitzer G, Rüegg JC, Flockerzi V, Hofmann F (1982) cGMP-dependent protein kinase decreases calcium sensitivity of skinned cardiac fibers. FEBS Lett 149(2):171–175. https://doi.org/10.1016/0014-5793(82)81095-8
Pfrieger FW (2003) Role of cholesterol in synapse formation and function. Biochim Biophys Acta 1610(2):271–280. https://doi.org/10.1016/s0005-2736(03)00024-5
Phelan KD, Mahler HR (1997) Acute exposure to 25-hydroxy-cholesterol selectively reduces GABAb and not GABAa receptor-mediated synaptic inhibition. Biochem Biophys Res Commun 237(1):68–73. https://doi.org/10.1006/bbrc.1997.7070
Pinard A, Robitaille R (2008) Nitric oxide dependence of glutamate-mediated modulation at a vertebrate neuromuscular junction. Eur J Neurosci 28(3):577–587. https://doi.org/10.1111/j.1460-9568.2008.06355.x
Pirie E, Oh CK, Zhang X, Han X, Cieplak P, Scott HR, Deal AK, Ghatak S, Martinez FJ, Yeo GW, Yates JR 3rd, Nakamura T, Lipton SA (2021) S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proc Natl Acad Sci U S A 118(11). https://doi.org/10.1073/pnas.2021368118
Popiolek M, Izumi Y, Hopper AT, Dai J, Miller S, Shu HJ, Zorumski CF, Mennerick S (2020) Effects of CYP46A1 inhibition on long-term-depression in hippocampal slices ex vivo and 24S-hydroxycholesterol levels in mice in vivo. Front Mol Neurosci 13:568641. https://doi.org/10.3389/fnmol.2020.568641
Prasanthi JR, Larson T, Schommer J, Ghribi O (2011) Silencing GADD153/CHOP gene expression protects against Alzheimer’s disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus. PLoS One 6(10):e26420. https://doi.org/10.1371/journal.pone.0026420
Pristera A, Baker MD, Okuse K (2012) Association between tetrodotoxin resistant channels and lipid rafts regulates sensory neuron excitability. PLoS One 7(8):e40079. https://doi.org/10.1371/journal.pone.0040079
Pucadyil TJ, Shrivastava S, Chattopadhyay A (2005) Membrane cholesterol oxidation inhibits ligand binding function of hippocampal serotonin(1A) receptors. Biochem Biophys Res Commun 331(2):422–427. https://doi.org/10.1016/j.bbrc.2005.03.178
Puglielli L, Friedlich AL, Setchell KD, Nagano S, Opazo C, Cherny RA, Barnham KJ, Wade JD, Melov S, Kovacs DM, Bush AI (2005) Alzheimer disease beta-amyloid activity mimics cholesterol oxidase. J Clin Invest 115(9):2556–2563. https://doi.org/10.1172/JCI23610
Radosevic M, Planaguma J, Mannara F, Mellado A, Aguilar E, Sabater L, Landa J, Garcia-Serra A, Maudes E, Gasull X, Lewis M, Dalmau J (2022) Allosteric modulation of NMDARs reverses patients’ autoantibody effects in mice. Neurol Neuroimmunol Neuroinflamm 9(1). https://doi.org/10.1212/NXI.0000000000001122
Ramirez DM, Andersson S, Russell DW (2008) Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. J Comp Neurol 507(5):1676–1693. https://doi.org/10.1002/cne.21605
Ravel-Chapuis A, Vandromme M, Thomas JL, Schaeffer L (2007) Postsynaptic chromatin is under neural control at the neuromuscular junction. EMBO J 26(4):1117–1128. https://doi.org/10.1038/sj.emboj.7601572
Rios R, Jablonka-Shariff A, Broberg C, Snyder-Warwick AK (2021) Macrophage roles in peripheral nervous system injury and pathology: Allies in neuromuscular junction recovery. Mol Cell Neurosci 111:103590. https://doi.org/10.1016/j.mcn.2021.103590
Rizzoli SO, Betz WJ (2005) Synaptic vesicle pools. Nat Rev Neurosci 6(1):57–69. https://doi.org/10.1038/nrn1583
Rovini A, Gurnev PA, Beilina A, Queralt-Martin M, Rosencrans W, Cookson MR, Bezrukov SM, Rostovtseva TK (2019) Molecular mechanism of olesoxime-mediated neuroprotection through targeting alpha-synuclein interaction with mitochondrial VDAC. Cell Mol Life Sci. https://doi.org/10.1007/s00018-019-03386-w
Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T (2009) Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem 78:1017–1040. https://doi.org/10.1146/annurev.biochem.78.072407.103859
Saadane A, Petrov A, Mast N, El-Darzi N, Dao T, Alnemri A, Song Y, Dunaief JL, Pikuleva IA (2018) Mechanisms that minimize retinal impact of apolipoprotein E absence. J Lipid Res 59(12):2368–2382. https://doi.org/10.1194/jlr.M090043
Sabirov RZ, Merzlyak PG (2012) Plasmalemmal VDAC controversies and maxi-anion channel puzzle. Biochim Biophys Acta 1818(6):1570–1580. https://doi.org/10.1016/j.bbamem.2011.09.024
Saheki Y, De Camilli P (2012) Synaptic vesicle endocytosis. Cold Spring Harb Perspect Biol 4(9):a005645. https://doi.org/10.1101/cshperspect.a005645
Salamone A, Terrone G, Di Sapia R, Balosso S, Ravizza T, Beltrame L, Craparotta I, Mannarino L, Cominesi SR, Rizzi M, Pauletti A, Marchini S, Porcu L, Zimmer TS, Aronica E, During M, Abrahams B, Kondo S, Nishi T, Vezzani A (2022) Cholesterol 24-hydroxylase is a novel pharmacological target for anti-ictogenic and disease modification effects in epilepsy. Neurobiol Dis 173:105835. https://doi.org/10.1016/j.nbd.2022.105835
Salen G, Polito A (1972) Biosynthesis of 5α-cholestan-3β-ol in cerebrotendinous xanthomatosis. J Clin Invest 51(1):134–140. https://doi.org/10.1172/jci106783
Sandebring-Matton A, Goikolea J, Bjorkhem I, Paternain L, Kemppainen N, Laatikainen T, Ngandu T, Rinne J, Soininen H, Cedazo-Minguez A, Solomon A, Kivipelto M (2021) 27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial. Alzheimers Res Ther 13(1):56. https://doi.org/10.1186/s13195-021-00790-y
Sansevrino R, Hoffmann C, Milovanovic D (2023) Condensate biology of synaptic vesicle clusters. Trends Neurosci. https://doi.org/10.1016/j.tins.2023.01.001
Sasaki S, Shibata N, Iwata M (2001) Neuronal nitric oxide synthase immunoreactivity in the spinal cord in amyotrophic lateral sclerosis. Acta Neuropathol 101(4):351–357. https://doi.org/10.1007/s004010000282
Scanlon SM, Williams DC, Schloss P (2001) Membrane cholesterol modulates serotonin transporter activity. Biochemistry 40(35):10507–10513. https://doi.org/10.1021/bi010730z
Serdiuk T, Manna M, Zhang C, Mari SA, Kulig W, Pluhackova K, Kobilka BK, Vattulainen I, Muller DJ (2022) A cholesterol analog stabilizes the human beta(2)-adrenergic receptor nonlinearly with temperature. Sci Signal 15(737):eabi7031. https://doi.org/10.1126/scisignal.abi7031
Shackleford G, Makoukji J, Grenier J, Liere P, Meffre D, Massaad C (2013) Differential regulation of Wnt/beta-catenin signaling by Liver X Receptors in Schwann cells and oligodendrocytes. Biochem Pharmacol 86(1):106–114. https://doi.org/10.1016/j.bcp.2013.02.036
Shafaati M, Olin M, Bavner A, Pettersson H, Rozell B, Meaney S, Parini P, Bjorkhem I (2011) Enhanced production of 24S-hydroxycholesterol is not sufficient to drive liver X receptor target genes in vivo. J Intern Med 270(4):377–387. https://doi.org/10.1111/j.1365-2796.2011.02389.x
Shang M, Cappellesso F, Amorim R, Serneels J, Virga F, Eelen G, Carobbio S, Rincon MY, Maechler P, De Bock K, Ho PC, Sandri M, Ghesquiere B, Carmeliet P, Di Matteo M, Berardi E, Mazzone M (2020) Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Nature 587(7835):626–631. https://doi.org/10.1038/s41586-020-2857-9
Sharma S, Prasanthi RPJ, Schommer E, Feist G, Ghribi O (2008) Hypercholesterolemia-induced Abeta accumulation in rabbit brain is associated with alteration in IGF-1 signaling. Neurobiol Dis 32(3):426–432. https://doi.org/10.1016/j.nbd.2008.08.002
Shen C, Zhou J, Wang X, Yu XY, Liang C, Liu B, Pan X, Zhao Q, Song JL, Wang J, Bao M, Wu C, Li Y, Song YH (2017) Angiotensin-II-induced muscle wasting is mediated by 25-hydroxycholesterol via GSK3beta signaling pathway. EBioMedicine 16:238–250. https://doi.org/10.1016/j.ebiom.2017.01.040
Shi Q, Li M, Mika D, Fu Q, Kim S, Phan J, Shen A, Vandecasteele G, Xiang YK (2017) Heterologous desensitization of cardiac β-adrenergic signal via hormone-induced βAR/arrestin/PDE4 complexes. Cardiovasc Res 113(6):656–670. https://doi.org/10.1093/cvr/cvx036
Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, Iwata K, Matsumoto K, Wakuda T, Kameno Y, Suzuki K, Tsujii M, Nakamura K, Takei N, Mori N (2011) Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PLoS One 6(10):e25340. https://doi.org/10.1371/journal.pone.0025340
Smiljanic K, Lavrnja I, Mladenovic Djordjevic A, Ruzdijic S, Stojiljkovic M, Pekovic S, Kanazir S (2010) Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. Histochem Cell Biol 134(2):159–169. https://doi.org/10.1007/s00418-010-0718-6
Sodero AO (2021) 24S-hydroxycholesterol: Cellular effects and variations in brain diseases. J Neurochem 157(4):899–918. https://doi.org/10.1111/jnc.15228
Sodero AO, Vriens J, Ghosh D, Stegner D, Brachet A, Pallotto M, Sassoe-Pognetto M, Brouwers JF, Helms JB, Nieswandt B, Voets T, Dotti CG (2012) Cholesterol loss during glutamate-mediated excitotoxicity. EMBO J 31(7):1764–1773. https://doi.org/10.1038/emboj.2012.31
Solger J, Heinemann U, Behr J (2005) Electrical and chemical long-term depression do not attenuate low-Mg2+-induced epileptiform activity in the entorhinal cortex. Epilepsia 46(4):509–516. https://doi.org/10.1111/j.0013-9580.2005.41204.x
Solsona-Vilarrasa E, Fucho R, Torres S, Nunez S, Nuno-Lambarri N, Enrich C, Garcia-Ruiz C, Fernandez-Checa JC (2019) Cholesterol enrichment in liver mitochondria impairs oxidative phosphorylation and disrupts the assembly of respiratory supercomplexes. Redox Biol 24:101214. https://doi.org/10.1016/j.redox.2019.101214
Spillmann F, Van Linthout S, Miteva K, Lorenz M, Stangl V, Schultheiss HP, Tschope C (2014) LXR agonism improves TNF-alpha-induced endothelial dysfunction in the absence of its cholesterol-modulating effects. Atherosclerosis 232(1):1–9. https://doi.org/10.1016/j.atherosclerosis.2013.10.001
Stein CA, Colombini M (2008) Specific VDAC inhibitors: phosphorothioate oligonucleotides. J Bioenerg Biomembr 40(3):157–162. https://doi.org/10.1007/s10863-008-9139-9
Sun MY, Izumi Y, Benz A, Zorumski CF, Mennerick S (2016) Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices. J Neurophysiol 115(3):1263–1272. https://doi.org/10.1152/jn.00890.2015
Sun MY, Taylor A, Zorumski CF, Mennerick S (2017) 24S-hydroxycholesterol and 25-hydroxycholesterol differentially impact hippocampal neuronal survival following oxygen-glucose deprivation. PLoS One 12(3):e0174416. https://doi.org/10.1371/journal.pone.0174416
Sunico CR, Dominguez G, Garcia-Verdugo JM, Osta R, Montero F, Moreno-Lopez B (2011) Reduction in the motoneuron inhibitory/excitatory synaptic ratio in an early-symptomatic mouse model of amyotrophic lateral sclerosis. Brain Pathol 21(1):1–15. https://doi.org/10.1111/j.1750-3639.2010.00417.x
Sytchev VI, Odnoshivkina YG, Ursan RV, Petrov AM (2017) Oxysterol, 5alpha-cholestan-3-one, modulates a contractile response to beta2-adrenoceptor stimulation in the mouse atria: Involvement of NO signaling. Life Sci 188:131–140. https://doi.org/10.1016/j.lfs.2017.09.006
Tajima N, Xiaoyan L, Taniguchi M (1864) Kato N (2019) 24S-hydroxycholesterol alters activity of large-conductance Ca(2+)-dependent K(+) (slo1 BK) channel through intercalation into plasma membrane. Biochim Biophys Acta Mol Cell Biol Lipids 10:1525–1535. https://doi.org/10.1016/j.bbalip.2019.05.010
Takamori S, Holt M, Stenius K, Lemke EA, Gronborg M, Riedel D, Urlaub H, Schenck S, Brugger B, Ringler P, Muller SA, Rammner B, Grater F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmuller H, Heuser J, Wieland F, Jahn R (2006) Molecular anatomy of a trafficking organelle. Cell 127(4):831–846. https://doi.org/10.1016/j.cell.2006.10.030
Tang L, Wang Y, Leng T, Sun H, Zhou Y, Zhu W, Qiu P, Zhang J, Lu B, Yan M, Chen W, Su X, Yin W, Huang Y, Hu H, Yan G (2015) Cholesterol metabolite cholestane-3beta,5alpha,6beta-triol suppresses epileptic seizures by negative modulation of voltage-gated sodium channels. Steroids 98:166–172. https://doi.org/10.1016/j.steroids.2014.12.025
Tang L, Yan M, Leng T, Yin W, Cai S, Duan S, Zhu W, Lin S, Huang J, Yan G, Zheng G, Chen Y (2018) Cholestane-3beta, 5alpha, 6beta-triol suppresses neuronal hyperexcitability via binding to voltage-gated sodium channels. Biochem Biophys Res Commun 496(1):95–100. https://doi.org/10.1016/j.bbrc.2018.01.004
Tang W, Liu D, Traynelis SF, Yuan H (2020) Positive allosteric modulators that target NMDA receptors rectify loss-of-function GRIN variants associated with neurological and neuropsychiatric disorders. Neuropharmacology 177:108247. https://doi.org/10.1016/j.neuropharm.2020.108247
Tang W, Beckley JT, Zhang J, Song R, Xu Y, Kim S, Quirk MC, Robichaud AJ, Diaz ES, Myers SJ, Doherty JJ, Ackley MA, Traynelis SF, Yuan H (2023) Novel neuroactive steroids as positive allosteric modulators of NMDA receptors: mechanism, site of action, and rescue pharmacology on GRIN variants associated with neurological conditions. Cell Mol Life Sci 80(2):42. https://doi.org/10.1007/s00018-022-04667-7
Torres S, Garcia-Ruiz CM, Fernandez-Checa JC (2019) Mitochondrial cholesterol in Alzheimer’s disease and Niemann-Pick type C disease. Front Neurol 10:1168. https://doi.org/10.3389/fneur.2019.01168
Troncone L, Luciani M, Coggins M, Wilker EH, Ho CY, Codispoti KE, Frosch MP, Kayed R, Del Monte F (2016) Abeta amyloid pathology affects the hearts of patients with Alzheimer’s disease: mind the heart. J Am Coll Cardiol 68(22):2395–2407. https://doi.org/10.1016/j.jacc.2016.08.073
Tsentsevitsky AN, Zakyrjanova GF, Petrov AM (2020) Cadmium desynchronizes neurotransmitter release in the neuromuscular junction: Key role of ROS. Free Radic Biol Med 155:19–28. https://doi.org/10.1016/j.freeradbiomed.2020.05.017
Tsentsevitsky AN, Gafurova CR, Mukhutdinova KA, Giniatullin AR, Fedorov NS, Malomouzh AI, Petrov AM (2023) Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions. Life Sci 318:121507. https://doi.org/10.1016/j.lfs.2023.121507
Tyganov SA, Mochalova E, Belova S, Sharlo K, Rozhkov S, Kalashnikov V, Turtikova O, Mirzoev T, Shenkman B (2021) Plantar mechanical stimulation attenuates protein synthesis decline in disused skeletal muscle via modulation of nitric oxide level. Sci Rep 11(1):9806. https://doi.org/10.1038/s41598-021-89362-6
Ullrich C, Pirchl M, Humpel C (2010) Effects of cholesterol and its 24S-OH and 25-OH oxysterols on choline acetyltransferase-positive neurons in brain slices. Pharmacology 86(1):15–21. https://doi.org/10.1159/000314333
Unsworth AJ, Flora GD, Gibbins JM (2018) Non-genomic effects of nuclear receptors: insights from the anucleate platelet. Cardiovasc Res 114(5):645–655. https://doi.org/10.1093/cvr/cvy044
Ursan R, Odnoshivkina UG, Petrov AM (2019) Membrane cholesterol oxidation downregulates atrial beta-adrenergic responses in ROS-dependent manner. Cell Signal 67:109503. https://doi.org/10.1016/j.cellsig.2019.109503
Ute P, Ulla A, Magnus H, Wolfgang S, Steve M, Ingemar B (2007) On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid Res 48(5):1167–1174. https://doi.org/10.1194/jlr.M700027-JLR200
van der Kant R, Goldstein LSB, Ossenkoppele R (2020) Amyloid-beta-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci 21(1):21–35. https://doi.org/10.1038/s41583-019-0240-3
Vejux A, Abed-Vieillard D, Hajji K, Zarrouk A, Mackrill JJ, Ghosh S, Nury T, Yammine A, Zaibi M, Mihoubi W, Bouchab H, Nasser B, Grosjean Y, Lizard G (2020) 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity. Biochem Pharmacol 173:113648. https://doi.org/10.1016/j.bcp.2019.113648
Verma S, Khurana S, Vats A, Sahu B, Ganguly NK, Chakraborti P, Gourie-Devi M, Taneja V (2022) Neuromuscular junction dysfunction in amyotrophic lateral sclerosis. Mol Neurobiol 59(3):1502–1527. https://doi.org/10.1007/s12035-021-02658-6
Walder KK, Ryan SB, Bzdega T, Olszewski RT, Neale JH, Lindgren CA (2013) Immunohistological and electrophysiological evidence that N-acetylaspartylglutamate is a co-transmitter at the vertebrate neuromuscular junction. Eur J Neurosci 37(1):118–129. https://doi.org/10.1111/ejn.12027
Wang Y, An Y, Zhang D, Yu H, Zhang X, Wang Y, Tao L, Xiao R (2019) 27-Hydroxycholesterol alters synaptic structural and functional plasticity in hippocampal neuronal cultures. J Neuropathol Exp Neurol 78(3):238–247. https://doi.org/10.1093/jnen/nlz002
Wang Y, Li X, Ren S (2020) Cholesterol metabolites 25-hydroxycholesterol and 25-hydroxycholesterol 3-sulfate are potent paired regulators: from discovery to clinical usage. Metabolites 11(1). https://doi.org/10.3390/metabo11010009
Warikoo N, Brunwasser SJ, Benz A, Shu HJ, Paul SM, Lewis M, Doherty J, Quirk M, Piccio L, Zorumski CF, Day GS, Mennerick S (2018) Positive allosteric modulation as a potential therapeutic strategy in anti-NMDA receptor encephalitis. J Neurosci 38(13):3218–3229. https://doi.org/10.1523/JNEUROSCI.3377-17.2018
Wei X, Nishi T, Kondou S, Kimura H, Mody I (2019) Preferential enhancement of GluN2B-containing native NMDA receptors by the endogenous modulator 24S-hydroxycholesterol in hippocampal neurons. Neuropharmacology 148:11–20. https://doi.org/10.1016/j.neuropharm.2018.12.028
Wilding TJ, Lopez MN, Huettner JE (2016) Chimeric glutamate receptor subunits reveal the transmembrane domain is sufficient for NMDA receptor pore properties but some positive allosteric modulators require additional domains. J Neurosci 36(34):8815–8825. https://doi.org/10.1523/JNEUROSCI.0345-16.2016
Wong MY, Lewis M, Doherty JJ, Shi Y, Cashikar AG, Amelianchik A, Tymchuk S, Sullivan PM, Qian M, Covey DF, Petsko GA, Holtzman DM, Paul SM, Luo W (2020) 25-Hydroxycholesterol amplifies microglial IL-1beta production in an apoE isoform-dependent manner. J Neuroinflamm 17(1):192. https://doi.org/10.1186/s12974-020-01869-3
Wood WG, Igbavboa U, Rao AM, Schroeder F, Avdulov NA (1995) Cholesterol oxidation reduces Ca(2+)+MG (2+)-ATPase activity, interdigitation, and increases fluidity of brain synaptic plasma membranes. Brain Res 683(1):36–42. https://doi.org/10.1016/0006-8993(95)00347-s
Wu Y, Dissing-Olesen L, MacVicar BA, Stevens B (2015) Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol 36(10):605–613. https://doi.org/10.1016/j.it.2015.08.008
Xia P, Chen HS, Zhang D, Lipton SA (2010) Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses. J Neurosci 30(33):11246–11250. https://doi.org/10.1523/JNEUROSCI.2488-10.2010
Xiang YK (2011) Compartmentalization of beta-adrenergic signals in cardiomyocytes. Circ Res 109(2):231–244. https://doi.org/10.1161/CIRCRESAHA.110.231340
Xue D, Wei C, Zhou Y, Wang K, Zhou Y, Chen C, Li Y, Sheng L, Lu B, Zhu Z, Cai W, Ning X, Li S, Qi T, Pi J, Lin S, Yan G, Huang Y, Yin W (2022) TRIOL inhibits rapid intracellular acidification and cerebral ischemic injury: the role of glutamate in neuronal metabolic reprogramming. ACS Chem Neurosci 13(14):2110–2121. https://doi.org/10.1021/acschemneuro.2c00119
Yammine A, Nury T, Vejux A, Latruffe N, Vervandier-Fasseur D, Samadi M, Greige-Gerges H, Auezova L, Lizard G (2020) Prevention of 7-ketocholesterol-induced overproduction of reactive oxygen species, mitochondrial dysfunction and cell death with major nutrients (polyphenols, omega3 and omega9 unsaturated fatty acids) of the Mediterranean diet on N2a neuronal cells. Molecules 25(10). https://doi.org/10.3390/molecules25102296
Yao Y, Sun S, Kong Q, Tong E (2006) 7β-hydroxycholesterol reduces the extent of reactive gliosis caused by iron deposition in the hippocampus but does not attenuate the iron-induced seizures in rats. Neuroscience 138(4):1097–1103. https://doi.org/10.1016/j.neuroscience.2005.12.011
Yawata I, Takeuchi H, Doi Y, Liang J, Mizuno T, Suzumura A (2008) Macrophage-induced neurotoxicity is mediated by glutamate and attenuated by glutaminase inhibitors and gap junction inhibitors. Life Sci 82(21–22):1111–1116. https://doi.org/10.1016/j.lfs.2008.03.010
Ye S, Zhong J, Huang J, Zhang S, Li H, Chen D, Li C (2020) (+)4-Cholesten-3-one promotes differentiation of neural stem cells into dopaminergic neurons through TET1 and FoxA2. Neurosci Lett 735:135239. https://doi.org/10.1016/j.neulet.2020.135239
Yue HY, Xu J (2015) Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse. J Neurochem 134(2):247–260. https://doi.org/10.1111/jnc.13129
Zaglia T, Mongillo M (2017) Cardiac sympathetic innervation, from a different point of (re)view. J Physiol 595(12):3919–3930. https://doi.org/10.1113/JP273120
Zakyrjanova GF, Gilmutdinov AI, Tsentsevitsky AN, Petrov AM (2020) Olesoxime, a cholesterol-like neuroprotectant restrains synaptic vesicle exocytosis in the mice motor nerve terminals: Possible role of VDACs. Biochim Biophys Acta Mol Cell Biol Lipids. https://doi.org/10.1016/j.bbalip.2020.158739
Zakyrjanova GF, Giniatullin AR, Mukhutdinova KA, Kuznetsova EA, Petrov AM (2021a) Early differences in membrane properties at the neuromuscular junctions of ALS model mice: Effects of 25-hydroxycholesterol. Life Sci 273:119300. https://doi.org/10.1016/j.lfs.2021.119300
Zakyrjanova GF, Tsentsevitsky AN, Kuznetsova EA, Petrov AM (2021b) Immune-related oxysterol modulates neuromuscular transmission via non-genomic liver X receptor-dependent mechanism. Free Radic Biol Med 174:121–134. https://doi.org/10.1016/j.freeradbiomed.2021.08.013
Zanos P, Gould TD (2018) Mechanisms of ketamine action as an antidepressant. Mol Psychiatry 23(4):801–811. https://doi.org/10.1038/mp.2017.255
Zefirov AL, Mukhametzyanov RD, Zakharov AV, Mukhutdinova KA, Odnoshivkina UG, Petrov AM (2020) Intracellular acidification suppresses synaptic vesicle mobilization in the motor nerve terminals. Acta Naturae 12(4):105–113. https://doi.org/10.32607/actanaturae.11054
Zhang DD, Yu HL, Ma WW, Liu QR, Han J, Wang H, Xiao R (2015) 27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain. Neuroscience 300:163–173. https://doi.org/10.1016/j.neuroscience.2015.05.022
Zhang X, Lv C, An Y, Liu Q, Rong H, Tao L, Wang Y, Wang Y, Xiao R (2018) Increased levels of 27-hydroxycholesterol induced by dietary cholesterol in brain contribute to learning and memory impairment in rats. Mol Nutr Food Res 62(3). https://doi.org/10.1002/mnfr.201700531
Zhang X, Xi Y, Yu H, An Y, Wang Y, Tao L, Wang Y, Liu W, Wang T, Xiao R (2019) 27-hydroxycholesterol promotes Abeta accumulation via altering Abeta metabolism in mild cognitive impairment patients and APP/PS1 mice. Brain Pathol 29(4):558–573. https://doi.org/10.1111/bpa.12698
Zhang J, Zhang F, Wu J, Li J, Yang Z, Yue J (2020) Glutamate affects cholesterol homeostasis within the brain via the up-regulation of CYP46A1 and ApoE. Toxicology 432:152381. https://doi.org/10.1016/j.tox.2020.152381
Zhao Y, Zhu M, Yu Y, Qiu L, Zhang Y, He L, Zhang J (2017) Brain REST/NRSF is not only a silent repressor but also an active protector. Mol Neurobiol 54(1):541–550. https://doi.org/10.1007/s12035-015-9658-4
Zheng S, Gray EE, Chawla G, Porse BT, O’Dell TJ, Black DL (2012) PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci 15(3):381–388, S381. https://doi.org/10.1038/nn.3026
Zhu YZ, Liu JW, Wang X, Jeong IH, Ahn YJ, Zhang CJ (2018) Anti-BACE1 and antimicrobial activities of steroidal compounds isolated from marine Urechis unicinctus. Mar Drugs 16(3). https://doi.org/10.3390/md16030094
Zorumski CF, Izumi Y (2012) NMDA receptors and metaplasticity: mechanisms and possible roles in neuropsychiatric disorders. Neurosci Biobehav Rev 36(3):989–1000. https://doi.org/10.1016/j.neubiorev.2011.12.011
Acknowledgments
I am grateful to my family for their continuous support. Many thanks to my collaborators and the numerous Researchers for insights regarding the multifaced roles of oxysterols in synaptic communications. I am grateful to Dr. Nicole El-Darzi (Case Western Reserve University) for her helpful discussion and comments on the chapter.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
This work was supported by the Russian Science Foundation, grant number [21-14-00044], https://rscf.ru/project/21-14-00044/.
Conflict of Interest
The author has no relevant financial or non-financial interests to disclose.
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Petrov, A.M. (2024). Oxysterols in Central and Peripheral Synaptic Communication. In: Lizard, G. (eds) Implication of Oxysterols and Phytosterols in Aging and Human Diseases. Advances in Experimental Medicine and Biology, vol 1440. Springer, Cham. https://doi.org/10.1007/978-3-031-43883-7_6
Download citation
DOI: https://doi.org/10.1007/978-3-031-43883-7_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-43882-0
Online ISBN: 978-3-031-43883-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)