Skip to main content

Advertisement

SpringerLink
Log in

Pathophysiological Roles of Intracellular Proteases in Neuronal Development and Neurological Diseases

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Proteases are classified into six distinct classes (cysteine, serine, threonine, aspartic, glutamic, and metalloproteases) on the basis of catalytic mechanism. The cellular control of protein quality senses misfolded or damaged proteins principally by selective ubiquitin-proteasome pathway and non-selective autophagy-lysosome pathway. The two pathways do not only maintain cell homeostasis physiologically, but also mediate necrosis and apoptosis pathologically. Proteasomes are threonine proteases, whereas cathepsins are lysosomal aspartic proteases. Calpains are non-lysosomal cysteine proteases and calcium-dependent papain-like enzyme. Calpains and cathepsins are involved in the neuronal necrosis, which are accidental cell death. Necrosis is featured by the disruption of plasma membranes and lysosomes, the loss of ATP and ribosomes, the lysis of cell and nucleus, and the caspase-independent DNA fragmentation. On the other hand, caspases are cysteine endoproteases and mediate neuronal cell death such as apoptosis and pyroptosis, which are programmed cell death. In the central nervous system, necroptosis, ferroptosis and autophagic cell death are also classified into programmed cell death. Neuronal apoptosis is characterized by cell shrinkage, plasma membrane blebbing, karyorrhexis, chromatin condensation, and DNA fragmentation. Necroptosis and pyroptosis are necrotic and lytic forms of programmed cell death, respectively. Although autophagy is involved in cell survival, it fails to maintain cellular homeostasis, resulting in autophagic cell death. Ferroptosis is induced by reactive oxygen species in excitotoxicity of glutamate and ischemia-reperfusion. Apoptosis and pyroptosis are dependent on caspase-3 and caspase-1, respectively. Autophagic cell death and necroptosis are dependent on calpain and cathepsin, respectively, but independent of caspase. Although apoptosis has been defined by the absence of morphological features of necrosis, the two deaths are both parts of a continuum. The intracellular proteases do not only maintain cell homeostasis but also regulate neuronal maturation during the development of embryonic brain. Furthermore, neurodegenerative diseases are caused by the impairment of quality control mechanisms for a proper folding and function of protein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

Abbreviations

AA:

Arachidonic acid

Aβ:

Amyloid β

ACD:

Autophagic cell death

AD:

Alzheimer’s disease

AIF:

Apoptosis-inducing factor

ALP:

Autophagy–lysosome pathway

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

ASC:

Apoptosis specific-like adaptor protein

Atg:

Autophagy-related genes

AVs:

Autophagic vacuoles

[Ca2+]i:

Intracellular calcium level

CARD:

Caspase recruitment domain

CJD:

Creutzfeldt–Jakob disease

CMA:

Chaperone-mediated autophagy

CNS:

Central nervous system

CRTH2:

Chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells

CTX :

Cerebral cortex

COX:

Cyclooxygenase

CycPGs:

Cyclopentenone prostaglandins

Cyt:

Cytochrome

DAMP:

Danger-associated molecular patterns

DISC:

Death-inducing signaling complex

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

FADD:

Fas-associated death domain

GPX4:

Glutathione peroxidase-4

GSH:

Glutathione

HD:

Huntington’s disease

HPC:

Hippocampus

JNK:

c-Jun N2-terminal kinase

LOX:

Lipoxygenase

L-VDCC:

L-type voltage-dependent Ca2+ channels

MAPK:

Mitogen-activated protein kinase

MCA:

Middle cerebral artery

mTOR:

Mammalian target of rapamycin

MLKL:

Mixed-lineage kinase domain-like protein

MPTP:

Mitochondrial permeability transition pore

NFTs:

Neurofibrillary tangles

NGF:

Nerve growth factor

NLR:

Nucleotide-binding oligomerization domain-like receptor

NOX:

NADPH oxygenase

NTRs:

Neurotrophic receptors

PAMP:

Pathogen-associated molecular patterns

PARP:

Poly(ADP-ribose) polymerase

PCD:

Programmed cell death

PD:

Parkinson’s disease

PI:

Propidium iodide

PI3K:

Phosphatidylinositol 3-kinase

PPARγ:

Peroxisome proliferator-activated receptor-γ

PrPC :

Cellular prion protein

PrPSc :

Scrapie prion protein

PRRs:

Pattern-recognition receptors

PS:

Phosphatidylserine

PUMA:

p53 upregulated modulator of apoptosis

ROS:

Reactive oxygen species

RIP:

Receptor-interacting protein

SOD:

Superoxide dismutase

sPLA2 :

Secreted phospholipase A2

STR:

Striatum

TNF-α:

Tumor necrosis factor α

TRAIL:

TNF-related apoptosis-inducing ligand

ULK1:

Unc-51 like autophagy activating kinase1

UPP:

Ubiquitin–proteasome pathway

UPR:

Unfolded protein response

VSC:

Ventral spinal cord

15d-PGJ2 :

15-deoxy-Δ12,14 prostaglandin J2

References

  1. Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12(9):814–822. https://doi.org/10.1038/ncb0910-814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rosello A, Warnes G, Meier UC (2012) Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die—that is the question. Clin Exp Immunol 168(1):52–57. https://doi.org/10.1111/j.1365-2249.2011.04544.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10(7):458–467. https://doi.org/10.1038/nrm2708

    Article  CAS  PubMed  Google Scholar 

  4. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492. https://doi.org/10.1146/annurev.ph.28.030166.002251

    Article  PubMed  Google Scholar 

  5. Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479. https://doi.org/10.1146/annurev.biochem.67.1.425

    Article  CAS  PubMed  Google Scholar 

  6. Ciechanover A (2006) The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting. Neurology 66(2 Suppl 1):S7–S19. https://doi.org/10.1212/01.wnl.0000192261.02023.b8

    Article  PubMed  Google Scholar 

  7. Lopez-Salon M, Alonso M, Vianna MR, Viola H, Mello e Souza T, Izquierdo I, Pasquini JM, Medina JH (2001) The ubiquitin–proteasome cascade is required for mammalian long-term memory formation. Eur J Neurosci 14(11):1820–1826

    Article  CAS  PubMed  Google Scholar 

  8. Tseng BP, Green KN, Chan JL, Blurton-Jones M, LaFerla FM (2008) Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging 29(11):1607–1618. https://doi.org/10.1016/j.neurobiolaging.2007.04.014

    Article  CAS  PubMed  Google Scholar 

  9. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Proc Natl Acad Sci U S A 82(12):4245–4249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65(3):351–355

    Article  CAS  PubMed  Google Scholar 

  11. Wang Z, Aris VM, Ogburn KD, Soteropoulos P, Figueiredo-Pereira ME (2006) Prostaglandin J2 alters pro-survival and pro-death gene expression patterns and 26 S proteasome assembly in human neuroblastoma cells. J Biol Chem 281(30):21377–21386. https://doi.org/10.1074/jbc.M601201200

    Article  CAS  PubMed  Google Scholar 

  12. Mullally JE, Moos PJ, Edes K, Fitzpatrick FA (2001) Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway. J Biol Chem 276(32):30366–30373. https://doi.org/10.1074/jbc.M102198200

    Article  CAS  PubMed  Google Scholar 

  13. Arnaud LT, Myeku N, Figueiredo-Pereira ME (2009) Proteasome-caspase-cathepsin sequence leading to tau pathology induced by prostaglandin J2 in neuronal cells. J Neurochem 110(1):328–342. https://doi.org/10.1111/j.1471-4159.2009.06142.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tovar-y-Romo LB, Penagos-Puig A, Ramirez-Jarquin JO (2016) Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. J Neurochem 136(1):13–27. https://doi.org/10.1111/jnc.13362

    Article  CAS  PubMed  Google Scholar 

  15. Weerasinghe P, Buja LM (2012) Oncosis: an important non-apoptotic mode of cell death. Exp Mol Pathol 93(3):302–308. https://doi.org/10.1016/j.yexmp.2012.09.018

    Article  CAS  PubMed  Google Scholar 

  16. Yagami T, Kohma H, Yamamoto Y (2012) L-type voltage-dependent calcium channels as therapeutic targets for neurodegenerative diseases. Curr Med Chem 19(28):4816–4827

    Article  CAS  PubMed  Google Scholar 

  17. Sahara S, Yamashima T (2010) Calpain-mediated Hsp70.1 cleavage in hippocampal CA1 neuronal death. Biochem Biophys Res Commun 393(4):806–811. https://doi.org/10.1016/j.bbrc.2010.02.087

    Article  CAS  PubMed  Google Scholar 

  18. Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH, Lenardo MJ (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304(5676):1500–1502. https://doi.org/10.1126/science.1096645

    Article  CAS  PubMed  Google Scholar 

  19. Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D et al (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25(3):1025–1040. https://doi.org/10.1128/MCB.25.3.1025-1040.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ullman E, Fan Y, Stawowczyk M, Chen HM, Yue Z, Zong WX (2008) Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress. Cell Death Differ 15(2):422–425. https://doi.org/10.1038/sj.cdd.4402234

    Article  CAS  PubMed  Google Scholar 

  21. Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1–RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137(6):1112–1123. https://doi.org/10.1016/j.cell.2009.05.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL et al (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19(1):107–120. https://doi.org/10.1038/cdd.2011.96

    Article  CAS  PubMed  Google Scholar 

  24. Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ (1995) Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 374(6524):736–739. https://doi.org/10.1038/374736a0

    Article  CAS  PubMed  Google Scholar 

  25. Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A 95(25):14681–14686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75(4):653–660

    Article  CAS  PubMed  Google Scholar 

  27. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148(7):2207–2216

    CAS  PubMed  Google Scholar 

  28. Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H et al (2008) BAX activation is initiated at a novel interaction site. Nature 455(7216):1076–1081. https://doi.org/10.1038/nature07396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Daugas E, Susin SA, Zamzami N, Ferri KF, Irinopoulou T, Larochette N, Prevost MC, Leber B et al (2000) Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J 14(5):729–739

    Article  CAS  PubMed  Google Scholar 

  30. Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12(6):611–620

    Article  CAS  PubMed  Google Scholar 

  31. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lanni C, Racchi M, Memo M, Govoni S, Uberti D (2012) p53 at the crossroads between cancer and neurodegeneration. Free Radic Biol Med 52(9):1727–1733. https://doi.org/10.1016/j.freeradbiomed.2012.02.034

    Article  CAS  PubMed  Google Scholar 

  33. Riley T, Sontag E, Chen P, Levine A (2008) Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9(5):402–412. https://doi.org/10.1038/nrm2395

    Article  CAS  PubMed  Google Scholar 

  34. Niizuma K, Endo H, Chan PH (2009) Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J Neurochem 109(Suppl 1):133–138. https://doi.org/10.1111/j.1471-4159.2009.05897.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kruse JP, Gu W (2009) Modes of p53 regulation. Cell 137(4):609–622. https://doi.org/10.1016/j.cell.2009.04.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tasdemir E, Maiuri MC, Galluzzi L, Vitale I, Djavaheri-Mergny M, D'Amelio M, Criollo A, Morselli E et al (2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10(6):676–687. https://doi.org/10.1038/ncb1730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137(6):1100–1111. https://doi.org/10.1016/j.cell.2009.05.021

    Article  CAS  PubMed  Google Scholar 

  38. Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325(5938):332–336. https://doi.org/10.1126/science.1172308

    Article  CAS  PubMed  Google Scholar 

  39. Wu XN, Yang ZH, Wang XK, Zhang Y, Wan H, Song Y, Chen X, Shao J et al (2014) Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis. Cell Death Differ 21(11):1709–1720. https://doi.org/10.1038/cdd.2014.77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54(1):133–146. https://doi.org/10.1016/j.molcel.2014.03.003

    Article  CAS  PubMed  Google Scholar 

  41. Kawahara A, Ohsawa Y, Matsumura H, Uchiyama Y, Nagata S (1998) Caspase-independent cell killing by Fas-associated protein with death domain. J Cell Biol 143(5):1353–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD et al (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4(5):313–321. https://doi.org/10.1038/nchembio.83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185(8):1481–1486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yagami T, Ueda K, Asakura K, Hata S, Kuroda T, Sakaeda T, Takasu N, Tanaka K et al (2002) Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis. Mol Pharmacol 61(1):114–126

    Article  CAS  PubMed  Google Scholar 

  45. Brennan MA, Cookson BT (2000) Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol 38(1):31–40

    Article  CAS  PubMed  Google Scholar 

  46. Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142. https://doi.org/10.1111/imr.12287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kepp O, Galluzzi L, Zitvogel L, Kroemer G (2010) Pyroptosis—a cell death modality of its kind? Eur J Immunol 40(3):627–630. https://doi.org/10.1002/eji.200940160

    Article  CAS  PubMed  Google Scholar 

  48. Hersh D, Monack DM, Smith MR, Ghori N, Falkow S, Zychlinsky A (1999) The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci U S A 96(5):2396–2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3):285–296

    Article  CAS  PubMed  Google Scholar 

  50. Tan S, Sagara Y, Liu Y, Maher P, Schubert D (1998) The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 141(6):1423–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E et al (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8(3):237–248. https://doi.org/10.1016/j.cmet.2008.07.005

    Article  CAS  PubMed  Google Scholar 

  52. Neitemeier S, Jelinek A, Laino V, Hoffmann L, Eisenbach I, Eying R, Ganjam GK, Dolga AM et al (2017) BID links ferroptosis to mitochondrial cell death pathways. Redox Biol 12:558–570. https://doi.org/10.1016/j.redox.2017.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tobaben S, Grohm J, Seiler A, Conrad M, Plesnila N, Culmsee C (2011) Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons. Cell Death Differ 18(2):282–292. https://doi.org/10.1038/cdd.2010.92

    Article  CAS  PubMed  Google Scholar 

  54. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072. https://doi.org/10.1016/j.cell.2012.03.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I et al (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447(7146):864–868. https://doi.org/10.1038/nature05859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Speer RE, Karuppagounder SS, Basso M, Sleiman SF, Kumar A, Brand D, Smirnova N, Gazaryan I et al (2013) Hypoxia-inducible factor prolyl hydroxylases as targets for neuroprotection by "antioxidant" metal chelators: from ferroptosis to stroke. Free Radic Biol Med 62:26–36. https://doi.org/10.1016/j.freeradbiomed.2013.01.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Denton D, Nicolson S, Kumar S (2012) Cell death by autophagy: facts and apparent artefacts. Cell Death Differ 19(1):87–95. https://doi.org/10.1038/cdd.2011.146

    Article  CAS  PubMed  Google Scholar 

  58. Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieslar-Pobuda A et al (2013) Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophys Acta 1833(9):2057–2069. https://doi.org/10.1016/j.bbamcr.2013.04.011

    Article  CAS  PubMed  Google Scholar 

  59. Tsujimoto Y, Shimizu S (2005) Another way to die: autophagic programmed cell death. Cell Death Differ 12(Suppl 2):1528–1534. https://doi.org/10.1038/sj.cdd.4401777

    Article  CAS  PubMed  Google Scholar 

  60. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741–752. https://doi.org/10.1038/nrm2239

    Article  CAS  PubMed  Google Scholar 

  61. Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, Kroemer G (2007) Cell death modalities: classification and pathophysiological implications. Cell Death Differ 14(7):1237–1243. https://doi.org/10.1038/sj.cdd.4402148

    Article  CAS  PubMed  Google Scholar 

  62. Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140(3):313–326. https://doi.org/10.1016/j.cell.2010.01.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736. https://doi.org/10.1146/annurev.neuro.24.1.677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294(5548):1945–1948. https://doi.org/10.1126/science.1065057

    Article  CAS  PubMed  Google Scholar 

  65. Bhakar AL, Howell JL, Paul CE, Salehi AH, Becker EB, Said F, Bonni A, Barker PA (2003) Apoptosis induced by p75NTR overexpression requires Jun kinase-dependent phosphorylation of bad. J Neurosci 23(36):11373–11381

    Article  CAS  PubMed  Google Scholar 

  66. Troy CM, Friedman JE, Friedman WJ (2002) Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases. J Biol Chem 277(37):34295–34302. https://doi.org/10.1074/jbc.M205167200

    Article  CAS  PubMed  Google Scholar 

  67. Coffey ET (2014) Nuclear and cytosolic JNK signalling in neurons. Nat Rev Neurosci 15(5):285–299. https://doi.org/10.1038/nrn3729

    Article  CAS  PubMed  Google Scholar 

  68. Bjorkblom B, Vainio JC, Hongisto V, Herdegen T, Courtney MJ, Coffey ET (2008) All JNKs can kill, but nuclear localization is critical for neuronal death. J Biol Chem 283(28):19704–19713. https://doi.org/10.1074/jbc.M707744200

    Article  CAS  PubMed  Google Scholar 

  69. Oppenheim RW (2001) Viktor Hamburger (1900–2001). Journey of a neuroembryologist to the end of the millennium and beyond. Neuron 31(2):179–190

    Article  CAS  PubMed  Google Scholar 

  70. Nijholt DA, De Kimpe L, Elfrink HL, Hoozemans JJ, Scheper W (2011) Removing protein aggregates: the role of proteolysis in neurodegeneration. Curr Med Chem 18(16):2459–2476

    Article  CAS  PubMed  Google Scholar 

  71. Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6(1):79–87. https://doi.org/10.1038/nrm1552

    Article  CAS  PubMed  Google Scholar 

  72. Agostini M, Tucci P, Melino G (2011) Cell death pathology: perspective for human diseases. Biochem Biophys Res Commun 414(3):451–455. https://doi.org/10.1016/j.bbrc.2011.09.081

    Article  CAS  PubMed  Google Scholar 

  73. Hellwig CT, Passante E, Rehm M (2011) The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies. Curr Mol Med 11(1):31–47

    Article  CAS  PubMed  Google Scholar 

  74. Ciechanover A (2017) Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin–proteasome system and onto human diseases and drug targeting. Best Pract Res Clin Haematol 30(4):341–355. https://doi.org/10.1016/j.beha.2017.09.001

    Article  PubMed  Google Scholar 

  75. Yagami T, Yamamoto Y, Koma H (2014) The role of secretory phospholipase a(2) in the central nervous system and neurological diseases. Mol Neurobiol 49(2):863–876. https://doi.org/10.1007/s12035-013-8565-9

    Article  CAS  PubMed  Google Scholar 

  76. Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S, Siddiqi FH, Jahreiss L, Fleming A et al (2008) Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat Chem Biol 4(5):295–305. https://doi.org/10.1038/nchembio.79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Uversky VN (2007) Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem 103(1):17–37. https://doi.org/10.1111/j.1471-4159.2007.04764.x

    Article  CAS  PubMed  Google Scholar 

  78. Griffith JS (1967) Self-replication and scrapie. Nature 215(5105):1043–1044

    Article  CAS  PubMed  Google Scholar 

  79. Andersen PM, Al-Chalabi A (2011) Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat Rev Neurol 7(11):603–615. https://doi.org/10.1038/nrneurol.2011.150

    Article  CAS  PubMed  Google Scholar 

  80. Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10(12):524–530

    Article  CAS  PubMed  Google Scholar 

  81. Lee S, Sato Y, Nixon RA (2011) Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer's-like axonal dystrophy. J Neurosci 31(21):7817–7830. https://doi.org/10.1523/JNEUROSCI.6412-10.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hollenbeck PJ (1993) Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport. J Cell Biol 121(2):305–315

    Article  CAS  PubMed  Google Scholar 

  83. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889. https://doi.org/10.1038/nature04724

    Article  CAS  PubMed  Google Scholar 

  84. Keller JN, Huang FF, Markesbery WR (2000) Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience 98(1):149–156

    Article  CAS  PubMed  Google Scholar 

  85. Guglielmo MA, Chan PT, Cortez S, Stopa EG, McMillan P, Johanson CE, Epstein M, Doberstein CE (1998) The temporal profile and morphologic features of neuronal death in human stroke resemble those observed in experimental forebrain ischemia: the potential role of apoptosis. Neurol Res 20(4):283–296

    Article  CAS  PubMed  Google Scholar 

  86. Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y (1995) Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15(2):1001–1011

    Article  CAS  PubMed  Google Scholar 

  87. Sauer D, Allegrini PR, Cosenti A, Pataki A, Amacker H, Fagg GE (1993) Characterization of the cerebroprotective efficacy of the competitive NMDA receptor antagonist CGP40116 in a rat model of focal cerebral ischemia: an in vivo magnetic resonance imaging study. J Cereb Blood Flow Metab 13(4):595–602. https://doi.org/10.1038/jcbfm.1993.77

    Article  CAS  PubMed  Google Scholar 

  88. Vieira M, Fernandes J, Carreto L, Anuncibay-Soto B, Santos M, Han J, Fernandez-Lopez A, Duarte CB et al (2014) Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3. Neurobiol Dis 68:26–36. https://doi.org/10.1016/j.nbd.2014.04.002

    Article  CAS  PubMed  Google Scholar 

  89. Chu X, Fu X, Zou L, Qi C, Li Z, Rao Y, Ma K (2007) Oncosis, the possible cell death pathway in astrocytes after focal cerebral ischemia. Brain Res 1149:157–164. https://doi.org/10.1016/j.brainres.2007.02.061

    Article  CAS  PubMed  Google Scholar 

  90. Umemura K, Kawai H, Ishihara H, Nakashima M (1995) Inhibitory effect of clopidogrel, vapiprost and argatroban on the middle cerebral artery thrombosis in the rat. Jpn J Pharmacol 67(3):253–258

    Article  CAS  PubMed  Google Scholar 

  91. Hallenbeck JM (1994) Blood-damaged tissue interaction in experimental brain ischemia. Acta Neurochir Suppl 60:233–237

    CAS  PubMed  Google Scholar 

  92. Li Y, Sharov VG, Jiang N, Zaloga C, Sabbah HN, Chopp M (1995) Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146(5):1045–1051

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Yagami T, Ueda K, Asakura K, Sakaeda T, Hata S, Kuroda T, Sakaguchi G, Itoh N et al (2003) Porcine pancreatic group IB secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels. Brain Res 960(1–2):71–80

    Article  CAS  PubMed  Google Scholar 

  94. Yagami T, Ueda K, Asakura K, Nakazato H, Hata S, Kuroda T, Sakaeda T, Sakaguchi G et al (2003) Human group IIA secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels in cultured rat cortical neurons. J Neurochem 85(3):749–758

    Article  CAS  PubMed  Google Scholar 

  95. Yagami T, Ueda K, Hata S, Kuroda T, Itoh N, Sakaguchi G, Okamura N, Sakaeda T et al (2005) S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase a(2)-induced apoptosis. Neuropharmacology 49(2):174–184. https://doi.org/10.1016/j.neuropharm.2005.02.011

    Article  CAS  PubMed  Google Scholar 

  96. Nicholls DG (2009) Mitochondrial calcium function and dysfunction in the central nervous system. Biochim Biophys Acta 1787(11):1416–1424. https://doi.org/10.1016/j.bbabio.2009.03.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG (2005) Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem 280(8):6447–6454. https://doi.org/10.1074/jbc.M413269200

    Article  CAS  PubMed  Google Scholar 

  98. Zhang WH, Wang X, Narayanan M, Zhang Y, Huo C, Reed JC, Friedlander RM (2003) Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc Natl Acad Sci U S A 100(26):16012–16017. https://doi.org/10.1073/pnas.2534856100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T et al (2004) The role of autophagy during the early neonatal starvation period. Nature 432(7020):1032–1036. https://doi.org/10.1038/nature03029

    Article  CAS  PubMed  Google Scholar 

  100. Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, Dunn RS, Vorhees CV et al (2006) Cerebral ischemia–hypoxia induces intravascular coagulation and autophagy. Am J Pathol 169(2):566–583. https://doi.org/10.2353/ajpath.2006.051066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K et al (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172(2):454–469. https://doi.org/10.2353/ajpath.2008.070876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Davila D, Torres-Aleman I (2008) Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell 19(5):2014–2025. https://doi.org/10.1091/mbc.E07-08-0811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wisniewski T, Frangione B (1996) Molecular biology of brain aging and neurodegenerative disorders. Acta Neurobiol Exp (Wars) 56(1):267–279

    CAS  Google Scholar 

  104. Giraldo E, Lloret A, Fuchsberger T, Vina J (2014) Abeta and tau toxicities in Alzheimer's are linked via oxidative stress-induced p38 activation: protective role of vitamin E. Redox Biol 2:873–877. https://doi.org/10.1016/j.redox.2014.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med 8(6):595–608. https://doi.org/10.15252/emmm.201606210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci U S A 84(9):3033–3036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64(2):113–122

    Article  PubMed  Google Scholar 

  108. Yagami T (2006) Cerebral arachidonate cascade in dementia: Alzheimer's disease and vascular dementia. Curr Neuropharmacol 4(1):87–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lin TN, Wang Q, Simonyi A, Chen JJ, Cheung WM, He YY, Xu J, Sun AY et al (2004) Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain. J Neurochem 90(3):637–645

    Article  CAS  PubMed  Google Scholar 

  110. Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, Simonyi A, Sun GY (2006) Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease. J Neuroinflammation 3:28. https://doi.org/10.1186/1742-2094-3-28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci 31(9):454–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K (1997) Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals. J Neurochem 68(1):265–271

    Article  CAS  PubMed  Google Scholar 

  113. Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE (1992) Beta-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12(2):376–389

    Article  CAS  PubMed  Google Scholar 

  114. Ueda K, Fukui Y, Kageyama H (1994) Amyloid beta protein-induced neuronal cell death: neurotoxic properties of aggregated amyloid beta protein. Brain Res 639(2):240–244

    Article  CAS  PubMed  Google Scholar 

  115. Viola HM, Arthur PG, Hool LC (2007) Transient exposure to hydrogen peroxide causes an increase in mitochondria-derived superoxide as a result of sustained alteration in L-type Ca2+ channel function in the absence of apoptosis in ventricular myocytes. Circ Res 100(7):1036–1044

    Article  CAS  PubMed  Google Scholar 

  116. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H et al (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767

    Article  CAS  PubMed  Google Scholar 

  117. Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, Zaccheo D, Odetti P et al (2000) Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun 268(2):642–646

    Article  CAS  PubMed  Google Scholar 

  118. Harada J, Sugimoto M (1999) Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842(2):311–323

    Article  CAS  PubMed  Google Scholar 

  119. Lee C, Park DW, Lee J, Lee TI, Kim YJ, Lee YS, Baek SH (2006) Secretory phospholipase A2 induces apoptosis through TNF-alpha and cytochrome c-mediated caspase cascade in murine macrophage RAW 264.7 cells. Eur J Pharmacol 536(1–2):47–53

    Article  CAS  PubMed  Google Scholar 

  120. Fahnestock M, Michalski B, Xu B, Coughlin MD (2001) The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 18(2):210–220. https://doi.org/10.1006/mcne.2001.1016

    Article  CAS  PubMed  Google Scholar 

  121. Sobottka B, Reinhardt D, Brockhaus M, Jacobsen H, Metzger F (2008) ProNGF inhibits NGF-mediated TrkA activation in PC12 cells. J Neurochem 107(5):1294–1303. https://doi.org/10.1111/j.1471-4159.2008.05690.x

    Article  CAS  PubMed  Google Scholar 

  122. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276(5321):2045–2047

    Article  CAS  PubMed  Google Scholar 

  123. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840. https://doi.org/10.1038/42166

    Article  CAS  PubMed  Google Scholar 

  124. Duarte MH, Tone LG, Soares LR, dos Santos SA (1990) Cytogenetic study of a case of childhood erythroleukemia. Cancer Genet Cytogenet 49(1):25–30

    Article  CAS  PubMed  Google Scholar 

  125. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216(4542):136–144

    Article  CAS  PubMed  Google Scholar 

  126. Saborio GP, Permanne B, Soto C (2001) Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411(6839):810–813. https://doi.org/10.1038/35081095

    Article  CAS  PubMed  Google Scholar 

  127. Boellaard JW, Kao M, Schlote W, Diringer H (1991) Neuronal autophagy in experimental scrapie. Acta Neuropathol 82(3):225–228

    Article  CAS  PubMed  Google Scholar 

  128. Yagami T, Koma H, Yamamoto Y (2016) Pathophysiological roles of cyclooxygenases and prostaglandins in the central nervous system. Mol Neurobiol 53(7):4754–4771. https://doi.org/10.1007/s12035-015-9355-3

    Article  CAS  PubMed  Google Scholar 

  129. Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD et al (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18(2):327–338

    Article  CAS  PubMed  Google Scholar 

  130. Leigh PN, Whitwell H, Garofalo O, Buller J, Swash M, Martin JE, Gallo JM, Weller RO et al (1991) Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114(Pt 2):775–788

    Article  PubMed  Google Scholar 

  131. Friedlander RM, Brown RH, Gagliardini V, Wang J, Yuan J (1997) Inhibition of ICE slows ALS in mice. Nature 388(6637):31. https://doi.org/10.1038/40299

    Article  CAS  PubMed  Google Scholar 

  132. Tovar YRLB, Tapia R (2010) VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3-K pathway and inhibition of p38MAPK. J Neurochem 115(5):1090–1101. https://doi.org/10.1111/j.1471-4159.2010.06766.x

    Article  CAS  Google Scholar 

  133. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985) Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44(6):559–577

    Article  CAS  PubMed  Google Scholar 

  134. Li H, Li SH, Johnston H, Shelbourne PF, Li XJ (2000) Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat Genet 25(4):385–389. https://doi.org/10.1038/78054

    Article  CAS  PubMed  Google Scholar 

  135. Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 27(11):2803–2820. https://doi.org/10.1111/j.1460-9568.2008.06310.x

    Article  PubMed  Google Scholar 

  136. Yagami T, Ueda K, Asakura K, Hayasaki-Kajiwara Y, Nakazato H, Sakaeda T, Hata S, Kuroda T et al (2002) Group IB secretory phospholipase A2 induces neuronal cell death via apoptosis. J Neurochem 81(3):449–461

    Article  CAS  PubMed  Google Scholar 

  137. Yagami T, Yamamoto Y, Koma H (2017) Physiological and pathological roles of 15-deoxy-Delta12,14-prostaglandin J2 in the central nervous system and neurological diseases. Mol Neurobiol 55:2227–2248. https://doi.org/10.1007/s12035-017-0435-4

    Article  CAS  PubMed  Google Scholar 

  138. Iwamoto N, Kobayashi K, Kosaka K (1989) The formation of prostaglandins in the postmortem cerebral cortex of Alzheimer-type dementia patients. J Neurol 236(2):80–84

    Article  CAS  PubMed  Google Scholar 

  139. Gaudet RJ, Alam I, Levine L (1980) Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. J Neurochem 35(3):653–658

    Article  CAS  PubMed  Google Scholar 

  140. Fitzpatrick FA, Wynalda MA (1983) Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro. J Biol Chem 258(19):11713–11718

    CAS  PubMed  Google Scholar 

  141. Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K (2002) 15-deoxy-delta 12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J Biol Chem 277(12):10459–10466. https://doi.org/10.1074/jbc.M110314200

    Article  CAS  PubMed  Google Scholar 

  142. Yagami T, Ueda K, Asakura K, Takasu N, Sakaeda T, Itoh N, Sakaguchi G, Kishino J et al (2003) Novel binding sites of 15-deoxy-Delta12,14-prostaglandin J2 in plasma membranes from primary rat cortical neurons. Exp Cell Res 291(1):212–227

    Article  CAS  PubMed  Google Scholar 

  143. Yagami T, Yamamoto Y, Koma H (2017) 15-deoxy-Delta12,14-prostaglandin J2 in neurodegenerative diseases and cancers. Oncotarget 8(6):9007–9008. https://doi.org/10.18632/oncotarget.14701

    Article  PubMed  PubMed Central  Google Scholar 

  144. Koma H, Yamamoto Y, Nishii A, Yagami T (2017) 15-deoxy-Delta12,14-prostaglandin J2 induced neurotoxicity via suppressing phosphoinositide 3-kinase. Neuropharmacology 113(Pt a):416–425. https://doi.org/10.1016/j.neuropharm.2016.10.017

    Article  CAS  PubMed  Google Scholar 

  145. Figueiredo-Pereira ME, Rockwell P, Schmidt-Glenewinkel T, Serrano P (2014) Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin–proteasome pathway and mitochondria to neurodegeneration. Front Mol Neurosci 7:104. https://doi.org/10.3389/fnmol.2014.00104

    Article  PubMed  Google Scholar 

  146. Asai A, Tanahashi N, Qiu JH, Saito N, Chi S, Kawahara N, Tanaka K, Kirino T (2002) Selective proteasomal dysfunction in the hippocampal CA1 region after transient forebrain ischemia. J Cereb Blood Flow Metab 22(6):705–710. https://doi.org/10.1097/00004647-200206000-00009

    Article  PubMed  Google Scholar 

  147. Kawasaki H, Murayama S, Tomonaga M, Izumiyama N, Shimada H (1987) Neurofibrillary tangles in human upper cervical ganglia. Morphological study with immunohistochemistry and electron microscopy. Acta Neuropathol 75(2):156–159

    Article  CAS  PubMed  Google Scholar 

  148. Love S, Saitoh T, Quijada S, Cole GM, Terry RD (1988) Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, pick bodies and Lewy bodies. J Neuropathol Exp Neurol 47(4):393–405

    Article  CAS  PubMed  Google Scholar 

  149. Kilic E, Kilic U, Wang Y, Bassetti CL, Marti HH, Hermann DM (2006) The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia. FASEB J 20(8):1185–1187. https://doi.org/10.1096/fj.05-4829fje

    Article  CAS  PubMed  Google Scholar 

  150. Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A (2001) Alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a beta-amyloid-induced neurotoxicity. J Biol Chem 276(17):13541–13546. https://doi.org/10.1074/jbc.M008035200

    Article  CAS  PubMed  Google Scholar 

  151. Sagi Y, Mandel S, Amit T, Youdim MB (2007) Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 25(1):35–44. https://doi.org/10.1016/j.nbd.2006.07.020

    Article  CAS  PubMed  Google Scholar 

  152. Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15(4):961–973

    Article  CAS  PubMed  Google Scholar 

  153. Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, Tsujimoto Y (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6(12):1221–1228. https://doi.org/10.1038/ncb1192

    Article  CAS  PubMed  Google Scholar 

  154. Yamamoto Y, Koma H, Yagami T (2015) Hydrogen peroxide mediated the neurotoxicity of an antibody against plasmalemmal neuronspecific enolase in primary cortical neurons. Neurotoxicology 49:86–93. https://doi.org/10.1016/j.neuro.2015.05.008

    Article  CAS  PubMed  Google Scholar 

  155. Yamamoto Y, Koma H, Yagami T (2015) Localization of 14-3-3delta/xi on the neuronal cell surface. Exp Cell Res 338(2):149–161. https://doi.org/10.1016/j.yexcr.2015.09.002

    Article  CAS  PubMed  Google Scholar 

  156. Yamamoto Y, Koma H, Nishii S, Yagami T (2017) Anti-heat shock 70 kDa protein antibody induced neuronal cell death. Biol Pharm Bull 40(4):402–412. https://doi.org/10.1248/bpb.b16-00641

    Article  CAS  PubMed  Google Scholar 

  157. Wang W, Gao C, Hou XY, Liu Y, Zong YY, Zhang GY (2004) Activation and involvement of JNK1/2 in hydrogen peroxide-induced neurotoxicity in cultured rat cortical neurons. Acta Pharmacol Sin 25(5):630–636

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work presented in the submitted manuscript was funded by Grant-in-Aid 17K08327 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Author information

Authors and Affiliations

  1. Himeji Dokkyo University, Himeji, Hyogo, Japan

    Tatsurou Yagami, Yasuhiro Yamamoto & Hiromi Koma

Authors
  1. Tatsurou Yagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhiro Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiromi Koma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatsurou Yagami.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yagami, T., Yamamoto, Y. & Koma, H. Pathophysiological Roles of Intracellular Proteases in Neuronal Development and Neurological Diseases. Mol Neurobiol 56, 3090–3112 (2019). https://doi.org/10.1007/s12035-018-1277-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-018-1277-4

Keywords

Search

Navigation