Skip to main content

Advertisement

SpringerLink
Log in

Role of Cytoskeletal Elements in Regulation of Synaptic Functions: Implications Toward Alzheimer’s Disease and Phytochemicals-Based Interventions

  • Reviews
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD), a multifactorial disease, is characterized by the accumulation of neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques. AD is triggered via several factors like alteration in cytoskeletal proteins, a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), amyloid precursor protein (APP), and post-translational modifications (PTMs) in the cytoskeletal elements. Owing to the major structural and functional role of cytoskeletal elements, like the organization of axon initial segmentation, dendritic spines, synaptic regulation, and delivery of cargo at the synapse; modulation of these elements plays an important role in AD pathogenesis; like Tau is a microtubule-associated protein that stabilizes the microtubules, and it also causes inhibition of nucleo-cytoplasmic transportation by disrupting the integrity of nuclear pore complex. One of the major cytoskeletal elements, actin and its dynamics, regulate the dendritic spine structure and functions; impairments have been documented towards learning and memory defects. The second major constituent of these cytoskeletal elements, microtubules, are necessary for the delivery of the cargo, like ion channels and receptors at the synaptic membranes, whereas actin-binding protein, i.e., Cofilin’s activation form rod-like structures, is involved in the formation of paired helical filaments (PHFs) observed in AD. Also, the glial cells rely on their cytoskeleton to maintain synaptic functionality. Thus, making cytoskeletal elements and their regulation in synaptic structure and function as an important aspect to be focused for better management and targeting AD pathology. This review advocates exploring phytochemicals and Ayurvedic plant extracts against AD by elucidating their neuroprotective mechanisms involving cytoskeletal modulation and enhancing synaptic plasticity. However, challenges include their limited bioavailability due to the poor solubility and the limited potential to cross the blood–brain barrier (BBB), emphasizing the need for targeted strategies to improve therapeutic efficacy.

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

Similar content being viewed by others

Data Availability

Being a review article, this is not applicable.

References

  1. Agostinho P, Cunha RA, Oliveira C (2010) Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 16(25):2766–2778

    Article  CAS  PubMed  Google Scholar 

  2. Muñoz-Lasso DC, Romá-Mateo C, Pallardó FV, Gonzalez-Cabo P (2020) Much more than a scaffold: cytoskeletal proteins in neurological disorders. Cells 9(2):358

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sept D (2007) Microtubule polymerization: one step at a time. CurrBiol 17:R764-766

    CAS  Google Scholar 

  4. Bamburg JR, Bernstein BW (2016) Actin dynamics and cofilin-actin rods in Alzheimer disease. Cytoskeleton 73(9):477–497

    Article  CAS  PubMed  Google Scholar 

  5. Walsh KP, Minamide LS, Kane SJ, Shaw AE, Brown DR, Pulford B, Bamburg JR (2014) Amyloid-β and proinflammatory cytokines utilize a prion protein-dependent pathway to activate NADPH oxidase and induce cofilin-actin rods in hippocampal neurons. PLoS ONE 9(4):e95995

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  6. Boutajangout A, Sigurdsson EM, Krishnamurthy PK (2011) Tau as a therapeutic target for Alzheimer’s disease. Curr Alzheimer Res 8(6):666–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Didonna A, Opal P (2019) The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders. Mol Neurodegener 14(1):1–10

    Article  Google Scholar 

  8. Rudrabhatla P, Jaffe H, Pant HC (2011) Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer’s NFTs. FASEB J 25:3896–3905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yao J, Hennessey T, Flynt A, Lai E, Beal MF, Lin MT (2010) MicroRNA-related cofilin abnormality in Alzheimer’s disease. PLoS ONE 5(12):e15546

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Walsh DM, Selkoe DJ (2004) Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron 44(1):181–193

    Article  CAS  PubMed  Google Scholar 

  11. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW, Morris JC (2001) Altered expression of synaptic proteins occurs early during progression of Alzheimer’s disease. Neurology 56(1):127–129

    Article  CAS  PubMed  Google Scholar 

  12. Parajuli LK, Tanaka S, Okabe S (2017) Insights into age-old questions of new dendritic spines: from form to function. Brain Res Bull 129:3–11

    Article  PubMed  Google Scholar 

  13. Vargas-Restrepo F, Sabogal-Guáqueta AM, Cardona-Gómez GP (2018) Quercetin ameliorates inflammation in CA1 hippocampal region in aged triple transgenic Alzheimer´ s disease mice model. Biomedica 38:62–69

    Google Scholar 

  14. O’Neil SD, Rácz B, Brown WE, Gao Y, Soderblom EJ, Yasuda R, Soderling SH (2021) Action potential-coupled Rho GTPase signaling drives presynaptic plasticity. Elife 10:e63756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang C, Rasband MN (2016) Cytoskeletal control of axon domain assembly and function. Curr Opin Neurobiol 39:116–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bucher M, Fanutza T, Mikhaylova M (2020) Cytoskeletal makeup of the synapse: shaft versus spine. Cytoskeleton 77(3–4):55–64

    Article  CAS  PubMed  Google Scholar 

  17. Goldman JE, Yen SH (1986) Cytoskeletal protein abnormalities in neurodegenerative diseases. Ann Neurol 19:209–223

    Article  CAS  PubMed  Google Scholar 

  18. Kaur P, Sharma S (2018) Recent advances in pathophysiology of traumatic brain injury. Curr Neuropharmacol 16:1224–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Medeiros R, Baglietto VD, LaFerla FM (2011) The role of tau in Alzheimer’s disease and related disorders. CNS NeurosciTher 17:514–524

    Article  CAS  Google Scholar 

  20. Galloway PG, Mulvihill P, Perry G (1992) Filaments of Lewy bodies contain insoluble cytoskeletal elements. Am J Pathol 140:809–822

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Cartier L, Galvez S, Gajdusek DC (1985) Familial clustering of the ataxic form of Creutzfeldt-Jakob disease with Hirano bodies. J Neurol Neurosurg Psychiatry 48:2348

    Article  Google Scholar 

  22. Klymkowsky MW, Plummer DJ (1985) Giant axonal neuropathy: a conditional mutation affecting cytoskeletal organization. J Cell Biol 100:245–250

    Article  CAS  PubMed  Google Scholar 

  23. Karima O, Riazi G, Yousefi R, Movahedi AAM (2010) The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study). Neurol Sci 31(3):315–320

    Article  PubMed  Google Scholar 

  24. Promsuban C, Limsuvan S, Akarasereenont P, Tilokskulchai K, Tapechum S, Pakaprot N (2017) Bacopa monnieri extract enhances learning-dependent hippocampal long-term synaptic potentiation. NeuroReport 28(16):1031–1035

    Article  PubMed  Google Scholar 

  25. Bourne JN, Harris KM (2011) Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP. Hippocampus 21(4):354–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hruska M, Henderson N, Le Marchand SJ, Jafri H, Dalva MB (2018) Synaptic nanomodules underlie the organization and plasticity of spine synapses. Nat Neurosci 21(5):671–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. MacGillavry HD, Song Y, Raghavachari S, Blanpied TA (2013) Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors. Neuron 78(4):615–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. MacGillavry HD, Kerr JM, Kassner J, Frost NA, Blanpied TA (2016) Shank-cortactin interactions control actin dynamics to maintain flexibility of neuronal spines and synapses. Eur J Neurosci 43(2):179–193

    Article  PubMed  Google Scholar 

  29. Matt L, Kim K, Hergarden AC, Patriarchi T, Malik ZA, Park DK, Chowdhury D, Buonarati OR, Henderson PB, Gökçek Saraç Ç, Zhang Y, Mohapatra D, Horne MC, Ames JB, Hell JW (2018) Α-actinin anchors PSD-95 at postsynaptic sites. Neuron 97(5):1094-1109.e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bär J, Kobler O, van Bommel B, Mikhaylova M (2016) Periodic F-actin structures shape the neck of dendritic spines. Sci Rep 6:37136

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  31. Mikhaylova M, Bär J, van Bommel B, Schätzle P, YuanXiang P, Raman R, Hradsky J, Konietzny A, Loktionov EY, Reddy PP, Lopez-Rojas J, Spilker C, Kobler O, Raza SA, Stork O, Hoogenraad CC, Kreutz MR (2018) Caldendrin directly couples postsynaptic calcium signals to actin remodeling in dendritic spines. Neuron 97(5):1110-1125.e14

    Article  CAS  PubMed  Google Scholar 

  32. He Y, Janssen WG, Vissavajjhala P, Morrison JH (1998) Synaptic distribution of GluR2 in hippocampal GABAergic interneurons and pyramidal cells: a double-label immunogold analysis. Exp Neurol 150(1):1–13

    Article  CAS  PubMed  Google Scholar 

  33. Konietzny A, González-Gallego J, Bar J, Perez-Alvarez A, Drakew A, Demmers JA, Mikhaylova M (2019) Myosin V regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons. J Cell Sci 132(16):jcs230177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Crosby KC, Gookin SE, Garcia JD, Hahm KM, Dell’Acqua ML, Smith KR (2019) Nanoscale subsynaptic domains underlie the organization of the inhibitory synapse. Cell Rep 26(12):3284-3297.e3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sheng M, Kim E (2011) The postsynaptic organization of synapses. Cold Spring Harb Perspect Biol 3(12):a005678

    Article  PubMed  PubMed Central  Google Scholar 

  36. Giesemann T, Schwarz G, Nawrotzki R, Berhörster K, Rothkegel M, Schlüter K, Schrader N, Schindelin H, Mendel RR, Kirsch J, Jockusch BM (2003) Complex formation between the postsynaptic scaffolding protein gephyrin, profilin, and Mena: a possible link to the microfilament system. J Neurosci 23(23):8330–8339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kneussel M, Loebrich S (2007) Trafficking and synaptic anchoring of ionotropic inhibitory neurotransmitter receptors. Biol Cell 99(6):297–309

    Article  CAS  PubMed  Google Scholar 

  38. Van Bommel B, Konietzny A, Kobler O, Bär J, Mikhaylova M (2019) F-actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes. EMBO J 38(15):e101183

    Article  PubMed  PubMed Central  Google Scholar 

  39. Esteves da Silva M, Adrian M, Schätzle P, Lipka J, Watanabe T, Cho S, Futai K, Wierenga CJ, Kapitein LC, Hoogenraad CC (2015) Positioning of AMPA receptor-containing endosomes regulates synapse architecture. Cell Rep 13(5):933–943

    Article  CAS  PubMed  Google Scholar 

  40. Ageta-Ishihara N, Miyata T, Ohshima C, Watanabe M, Sato Y, Hamamura Y, Kinoshita M (2013) Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation. Nat Commun 4(1):1–11

    Article  Google Scholar 

  41. Spiliotis ET (2018) Spatial effects - site-specific regulation of actin and microtubule organization by septin GTPases. J Cell Sci 131(1):jcs207555

    Article  MathSciNet  PubMed  PubMed Central  Google Scholar 

  42. Tyagarajan SK, Fritschy JM (2014) Gephyrin: a master regulator of neuronal function? Nat Rev Neurosci 15(3):141–156

    Article  CAS  PubMed  Google Scholar 

  43. Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED (2002) ProSAP/Shank proteins—a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J Neurochem 81(5):903–910

    Article  CAS  PubMed  Google Scholar 

  44. Bell RL, Hauser SR, McClintick J, Rahman S, Edenberg HJ, Szumlinski KK, McBride WJ (2016) Ethanol-associated changes in glutamate reward neurocircuitry: a minireview of clinical and preclinical genetic findings. Prog Mol Biol Transl Sci 137:41–85

    Article  PubMed  Google Scholar 

  45. Motz CT, Kabat V, Saxena T, Bellamkonda RV, Zhu C (2021) Neuromechanobiology: an expanding field driven by the force of greater focus. Adv Healthcare Mater 10(19):2100102

    Article  CAS  Google Scholar 

  46. Shintani T, Noda M (2008) Protein tyrosine phosphatase receptor type Z dephosphorylates TrkA receptors and attenuates NGF-dependent neurite outgrowth of PC12 cells. J Biochem 144(2):259–266

    Article  CAS  PubMed  Google Scholar 

  47. Wang PY, Seabold GK, Wenthold RJ (2008) Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth. Mol Cell Neurosci 39(1):83–94

    Article  PubMed  PubMed Central  Google Scholar 

  48. Borovac J, Bosch M, Okamoto K (2018) Regulation of actin dynamics during structural plasticity of dendritic spines: signaling messengers and actin-binding proteins. Mol Cell Neurosci 91:122–130

    Article  CAS  PubMed  Google Scholar 

  49. Bosch M, Castro J, Saneyoshi T, Matsuno H, Sur M, Hayashi Y (2014) Structural and molecular remodeling of dendritic spine substructures during long-term potentiation. Neuron 82(2):444–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27(10):1372–1384

    Article  CAS  PubMed  Google Scholar 

  51. Murphy-Royal C, Dupuis J, Groc L, Oliet SH (2017) Astroglial glutamate transporters in the brain: regulating neurotransmitter homeostasis and synaptic transmission. J Neurosci Res 95(11):2140–2151

    Article  CAS  PubMed  Google Scholar 

  52. St-Amour I, Bosoi CR, Paré I, Doss IA, Ignatius Arokia Doss PM, Rangachari M, Hébert SS, Calon F (2019) Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer’s disease. J Neuroinflammation 16(1):1–12

    Article  Google Scholar 

  53. Hotulainen P, Hoogenraad CC (2010) Actin in dendritic spines: connecting dynamics to function. J Cell Biol 189(4):619–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tada T, Simonetta A, Batterton M, Kinoshita M, Edbauer D, Sheng M (2007) Role of Septin cytoskeleton in spine morphogenesis and dendrite development in neurons. Curr Biol 17(20):1752–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ewers H, Tada T, Petersen JD, Racz B, Sheng M, Choquet D (2014) A septin-dependent diffusion barrier at dendritic spine necks. PLoS One 9(12):e113916

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  56. Xie Y, Vessey JP, Konecna A, Dahm R, Macchi P, Kiebler MA (2007) The GTP-binding protein Septin 7 is critical for dendrite branching and dendritic-spine morphology. Curr Biol 17(20):1746–1751

    Article  CAS  PubMed  Google Scholar 

  57. Yadav S, Oses-Prieto JA, Peters CJ, Zhou J, Pleasure SJ, Burlingame AL, Jan LY, Jan YN (2017) TAOK2 kinase mediates PSD95 stability and dendritic spine maturation through Septin7 phosphorylation. Neuron 93(2):379–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Marttinen M, Kurkinen KM, Soininen H, Haapasalo A, Hiltunen M (2015) Synaptic dysfunction and septin protein family members in neurodegenerative diseases. Mol Neurodegener 10:1–12

    Article  CAS  Google Scholar 

  59. Musunuri S, Wetterhall M, Ingelsson M, Lannfelt L, Artemenko K, Bergquist J, Shevchenko G (2014) Quantification of the brain proteome in Alzheimer’s disease using multiplexed mass spectrometry. J Proteome Res 13(4):2056–2068

    Article  CAS  PubMed  Google Scholar 

  60. Takehashi M, Alioto T, Stedeford T, Persad AS, Banasik M, Masliah E, Ueda K (2003) Septin 3 gene polymorphism in Alzheimer’s disease. Gene Expr J Liver Res 11(5–6):263–270

    Article  CAS  Google Scholar 

  61. Mantha AK, Dhiman M, Taglialatela G, Perez-Polo RJ, Mitra S (2012) Proteomic study of amyloid beta (25–35) peptide exposure to neuronal cells: impact on APE1/Ref-1’s protein–protein interaction. J Neurosci Res 90(6):1230–1239

    Article  CAS  PubMed  Google Scholar 

  62. Chen A, Liao WP, Lu Q, Wong WSF, Wong PH (2007) Upregulation of dihydropyrimidinase-related protein 2, spectrin α II chain, heat shock cognate protein 70 pseudogene 1 and tropomodulin 2 after focal cerebral ischemia in rats—a proteomics approach. Neurochem Int 50(7–8):1078–1086

    Article  CAS  PubMed  Google Scholar 

  63. Cox PR, Fowler V, Xu B, Sweatt JD, Paylor R, Zoghbi HY (2003) Mice lacking Tropomodulin-2 show enhanced long-term potentiation, hyperactivity, and deficits in learning and memory. Mol Cell Neurosci 23(1):1–12

    Article  CAS  PubMed  Google Scholar 

  64. Sinha S, Hoshino D, Hong NH, Kirkbride KC, Grega-Larson NE, Seiki M, Weaver AM (2016) Cortactin promotes exosome secretion by controlling branched actin dynamics. J Cell Biol 214(2):197–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, Zhao Y,  Zhao X, Wang X, Ma Y, Malkoc V, Chiang C, Deng W, Chen Y,  Fu Y, Kwak KJ,  Fan Y, Kang C, Yin C, Rhee J, Bertani P, Otero J Wu L, Kyuson, Yun Andrew S, Lee Wen, Jiang Lesheng, Teng Betty YS, Kim L, Lee J (2021) Author Correction: large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation Nature Biomedical Engineering 5(8) 944–945. https://doi.org/10.1038/s41551-021-00725-w

  66. Kaur S, Verma H, Dhiman M, Tell G, Gigli GL, Janes F, Mantha AK (2021) Brain exosomes: friend or foe in Alzheimer’s disease? Mol Neurobiol 58:6610–6624

    Article  CAS  PubMed  Google Scholar 

  67. Counil H, Krantic S (2020) Synaptic activity and (Neuro)inflammation in Alzheimer’s disease: could exosomes be an additional link? J Alzheimer’s Dis 74:1029–1043

    Article  Google Scholar 

  68. Ilan Y (2023) Microtubules as a potential platform for energy transfer in biological systems: a target for implementing individualized, dynamic variability patterns to improve organ function. Mol Cell Biochem 478(2):375–392

    Article  CAS  PubMed  Google Scholar 

  69. Kelliher MT, Saunders HA, Wildonger J (2019) Microtubule control of functional architecture in neurons. Curr Opin Neurobiol 57:39–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lim SS, Sammak PJ, Borisy GG (1989) Progressive and spatially differentiated stability of microtubules in developing neuronal cells. J Cell Biol 109(1):253–263

    Article  CAS  PubMed  Google Scholar 

  71. Verma H, Gangwar P, Yadav A, Yadav B, Rao R, Kaur S, ..., Mantha AK (2023) Understanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer’s disease. Mitochondrion 73:19–29

  72. Reddy PH (2011) Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer’s disease. Brain Res 1415:136–148

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ballatore C, Lee VMY, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8(9):663–672

    Article  CAS  PubMed  Google Scholar 

  74. Erez H, Shemesh OA, Spira ME (2014) Rescue of tau-induced synaptic transmission pathology by paclitaxel. Front Cell Neurosci 8:34

    Article  PubMed  PubMed Central  Google Scholar 

  75. Michaelis ML, Dobrowsky RT, Li G (2002) Tau neurofibrillary pathology and microtubule stability. J Mol Neurosci 19:289–293

    Article  CAS  PubMed  Google Scholar 

  76. Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS, ..., Brunden KR (2012) The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 32(11):3601–3611

  77. Lee VMY, Daughenbaugh R, Trojanowski JQ (1994) Microtubule stabilizing drugs for the treatment of Alzheimer’s disease. Neurobiology of Aging 15:87–89. https://doi.org/10.1016/0197-4580(94)90179-1

    Article  Google Scholar 

  78. Farhy-Tselnicker I, Allen NJ (2018) Astrocytes, neurons, synapses: a tripartite view on cortical circuit development. Neural Dev 13(1):1–12

    Article  Google Scholar 

  79. Bosson A, Boisseau S, Buisson A, Savasta M, Albrieux M (2015) Disruption of dopaminergic transmission remodels tripartite synapse morphology and astrocytic calcium activity within substantia nigra pars reticulata. Glia 63(4):673–683

    Article  PubMed  Google Scholar 

  80. Haseleu J, Anlauf E, Blaess S, Endl E, Derouiche A (2013) Studying subcellular detail in fixed astrocytes: dissociation of morphologically intact glial cells (DIMIGs). Front Cell Neurosci 7:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Murk K, Blanco Suarez EM, Cockbill LM, Banks P, Hanley JG (2013) The antagonistic modulation of Arp2/3 activity by N-WASP, WAVE2 and PICK1 defines dynamic changes in astrocyte morphology. J Cell Sci 126(17):3873–3883

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Jurga AM, Paleczna M, Kadluczka J, Kuter KZ (2021) Beyond the GFAP-astrocyte protein markers in the brain. Biomolecules 11(9):1361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Villablanca C, Vidal R, Gonzalez-Billault C (2023) Are cytoskeleton changes observed in astrocytes functionally linked to aging? Brain Res Bull 196:59–67

    Article  CAS  PubMed  Google Scholar 

  84. Kulijewicz-Nawrot M, Verkhratsky A, Chvatal A, Sykova E, Rodríguez JJ (2012) Astrocytic cytoskeletal atrophy in the medial prefrontal cortex of a triple transgenic mouse model of Alzheimer’s disease. J Anat 221(3):252–262

    Article  PubMed  PubMed Central  Google Scholar 

  85. Andoh M, Koyama R (2021) Microglia regulate synaptic development and plasticity. Dev Neurobiol 81(5):568–590

    Article  PubMed  PubMed Central  Google Scholar 

  86. Tremblay MÈ, Majewska AK (2011) A role for microglia in synaptic plasticity? Commun Integr Biol 4(2):220–222

    Article  PubMed  PubMed Central  Google Scholar 

  87. Bauer NG, Richter-Landsberg C, Ffrench-Constant C (2009) Role of the oligodendroglial cytoskeleton in differentiation and myelination. Glia 57(16):1691–1705

    Article  PubMed  Google Scholar 

  88. Perez C, Ziburkus J, Ullah G (2016) Analyzing and modeling the dysfunction of inhibitory neurons in Alzheimer’s disease. PLoS ONE 11(12):e0168800

    Article  PubMed  PubMed Central  Google Scholar 

  89. Kole MH, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ (2008) Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 11(2):178–186

    Article  CAS  PubMed  Google Scholar 

  90. Winckler B, Forscher P, Mellman I (1999) A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 397(6721):698–701

    Article  ADS  CAS  PubMed  Google Scholar 

  91. Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V (1998) AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 143(5):1295–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. D’Este E, Kamin D, Göttfert F, El-Hady A, Hell SW (2015) STED nanoscopy reveals the ubiquity of subcortical cytoskeleton periodicity in living neurons. Cell Rep 10(8):1246–1251

    Article  PubMed  Google Scholar 

  93. Leterrier C, Potier J, Caillol G, Debarnot C, Boroni FR, Dargent B (2015) Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold. Cell Rep 13(12):2781–2793

    Article  CAS  PubMed  Google Scholar 

  94. Sobotzik JM, Sie JM, Politi C, Del Turco D, Bennett V, Deller T, Schultz C (2009) AnkyrinG is required to maintain axo-dendritic polarity in vivo. Proc Natl Acad Sci USA 106(41):17564–17569

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  95. Van Beuningen SF, Will L, Harterink M, Chazeau A, Van Battum EY, Frias CP, Hoogenraad CC (2015) TRIM46 controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. Neuron 88(6):1208–1226

    Article  PubMed  Google Scholar 

  96. Wang C, Wei Z, Chen K, Ye F, Yu C, Bennett V, Zhang M (2014) Structural basis of diverse membrane target recognitions by ankyrins. Elife 3:e04353

    Article  PubMed  PubMed Central  Google Scholar 

  97. Lai A, Sisodia SS, Trowbridge IS (1995) Characterization of sorting signals in the β-amyloid precursor protein cytoplasmic domain. J Biol Chem 270(8):3565–3573

    Article  CAS  PubMed  Google Scholar 

  98. Pelucchi S, Stringhi R, Marcello E (2020) Dendritic spines in Alzheimer’s disease: how the actin cytoskeleton contributes to synaptic failure. Int J Mol Sci 21(3):908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Alzheimer’s, A (2016) Alzheimer’s disease facts and figures. Alzheimers Dement: J Alzheimer’s Assoc 12:459–509

    Article  Google Scholar 

  100. Weller J, Budson A (2018) Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research 7:1161–1170

  101. Choi YK, Qi RZ (2014) Assaying Microtubule Nucleation by the γ-Tubulin Ring Complex. In: Elsevier (ed) Methods in enzymology, Hong kong, China, 540:119–130

  102. Joshi HC (1993) Gamma-tubulin: the hub of cellular microtubule assemblies. BioEssays 15:637–643

    Article  CAS  PubMed  Google Scholar 

  103. Kapitein LC, Hoogenraad CC (2015) Building the neuronal microtubule cytoskeleton. Neuron 87:492–506

    Article  CAS  PubMed  Google Scholar 

  104. Tsai LH, Gleeson JG (2005) Nucleokinesis in neuronal migration. Neuron 46:383–388

    Article  CAS  PubMed  Google Scholar 

  105. Chevalier-Larsen E, Holzbaur EL (2006) Axonal transport and neurodegenerative disease. Biochim Biophys Acta 1762:1094–1108

    Article  CAS  PubMed  Google Scholar 

  106. Dubey J, Ratnakaran N, Koushika SP (2015) Neurodegeneration and microtubule dynamics: death by a thousand cuts. Front Cell Neurosci 9:343

    Article  PubMed  PubMed Central  Google Scholar 

  107. Lodish H, Berk A, Zipursky SL (2000) Kinesin, dynein, and intracellular transport. In: Freeman WH (ed) Molecular cell biology, 4th edn. New York: W. H. Freeman

  108. Bloom GS (2014) Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol 71:505–508

    Article  PubMed  Google Scholar 

  109. Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends PharmacolSci 12:383–388

    Article  CAS  Google Scholar 

  110. Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, Wisniewski HM, Alafuzoff I, Winblad B (1986) Defective brain microtubule assembly in Alzheimer’s disease. Lancet 2:421–426

    Article  CAS  PubMed  Google Scholar 

  111. Jouanne M, Rault S, Voisin-Chiret AS (2017) Tau protein aggregation in Alzheimer’s disease: an attractive target for the development of novel therapeutic agents. Eur J Med Chem 139:153–167

    Article  CAS  PubMed  Google Scholar 

  112. Kolarova M, García-Sierra F, Bartos A, Ricny J, Ripova D (2012) Structure and pathology of tau protein in Alzheimer disease. Int J Alzheimers Dis 2012:731526

    PubMed  PubMed Central  Google Scholar 

  113. Lovestone S, Reynolds CH, Latimer D, Davis DR, Anderton BH, Gallo JM, Hanger D, Mulot S, Marquardt B, Stabel S (1994) Alzheimer’s disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr Biol 4:1077–1086

    Article  CAS  PubMed  Google Scholar 

  114. Murphy MP, LeVine H (2010) Alzheimer’s Disease and the β-Amyloid Peptide. J Alzheimer’s Dis 19:311

    Article  Google Scholar 

  115. Fernandez-Valenzuela JJ, Sanchez-Varo R, Muñoz-Castro C, De Castro V, Sanchez-Mejias E, Navarro V, Jimenez S, Nuñez-Diaz C, Gomez-Arboledas A, Moreno-Gonzalez I, Vizuete M, Davila JC, Vitorica J, Gutierrez A (2020) Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer’s disease model. Sci Rep 10:14776

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  116. Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y, Cook C, Miller SJ, Dujardin S, Amaral AS, Grima JC, Bennett RE, Tepper K, DeTure M, Vanderburg CR, Corjuc BT, DeVos SL, Gonzalez JA, Chew J, Vidensky S, …, Hyman BT (2018) Tau protein disrupts nucleocytoplasmic transport in Alzheimer's disease. Neuron 99(5):925–940

  117. Lester E, Parker R (2018) The tau of nuclear-cytoplasmic transport. Neuron 99(5):869–871

    Article  CAS  PubMed  Google Scholar 

  118. Tripathi T, Prakash J, Shav-Tal Y (2018) Phospho-tau impairs nuclear-cytoplasmic transport. ACS Chem Neurosci 10(1):36–38

    Article  PubMed  Google Scholar 

  119. Dickson JR, Yoon H, Frosch MP, Hyman BT (2021) Cytoplasmic mislocalization of RNA polymerase II subunit RPB1 in Alzheimer disease is linked to pathologic tau. J Neuropathol Exp Neurol 80(6):530–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Dillon C, Goda Y (2005) The actin cytoskeleton: integrating form and function at the synapse. Annu Rev Neurosci 28:25–55

    Article  CAS  PubMed  Google Scholar 

  121. Dominguez R, Holmes KC (2011) Actin structure and function. Annu Rev Biophys 40:169–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Cesca F, Baldelli P, Valtorta F, Benfenati F (2010) The synapsins: key actors of synapse function and plasticity. Prog Neurobiol 91(4):313–348

    Article  CAS  PubMed  Google Scholar 

  123. Sudhof TC (2013) A molecular machine for neurotransmitter release: synaptotagmin and beyond. Nat Med 19(10):1227–1231

    Article  PubMed  Google Scholar 

  124. Xue R, Meng H, Yin J, Xia J, Hu Z, Liu H (2021) The role of calmodulin vs. synaptotagmin in exocytosis. Front Mol Neurosci 14:691363–691375

  125. Hohmann T, Dehghani F (2019) The cytoskeleton—a complex interacting meshwork. Cells 8(4):362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bamburg JR, Bernstein BW, Davis RC, Flynn KC, Goldsbury C, Jensen JR, Maloney MT, Marsden IT, Minamide LS, Pak CW, Shaw AE, Whiteman I, Wiggan O (2010) ADF/Cofilin-actin rods in neurodegenerative diseases. Curr Alzheimer Res 7:241–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Hirano A (1994) Hirano bodies and related neuronal inclusions. Neuropathol Appl Neurobiol 20:3–11

    Article  CAS  PubMed  Google Scholar 

  128. Minamide LS, Striegl AM, Boyle JA, Meberg PJ, Bamburg JR (2000) Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nat Cell Biol 2:628–636

    Article  CAS  PubMed  Google Scholar 

  129. Ostrowski M, Grzanka A, Izdebska M (2005) The role of actin in Alzheimer’s disease. Postepy Hig Med Dosw (Online) 59:224–228

    PubMed  Google Scholar 

  130. Yao J, Khan AN (2013) Involvement of actin pathology in Alzheimer’s disease. Cell Dev Biol 2:e121

    Google Scholar 

  131. Desale SE, Chinnathambi S (2021) Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease. Cell Commun Signal 19:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Chanda K, Jana NR, Mukhopadhyay D (2021) Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease. Sci Rep 11:19254

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  133. Leung HW, Foo G, Banumurthy G, Chai X, Ghosh S, Mitra-Ganguli T, VanDongen AM (2017) The effect of Bacopa monnieri on gene expression levels in SH-SY5Y human neuroblastoma cells. PLoS ONE 12(8):e0182984

    Article  PubMed  PubMed Central  Google Scholar 

  134. Bays JL, DeMali KA (2017) Vinculin in cell-cell and cell-matrix adhesions. Cell Mol Life Sci 74(16):2999–3009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Liu R, Jin JP (2016) Calponin isoforms CNN1, CNN2 and CNN3: regulators for actin cytoskeleton functions in smooth muscle and non-muscle cells. Gene 585(1):143–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. González-Sánchez M, Díaz T, Pascual C, Antequera D, Herrero-San Martín A, Llamas-Velasco S, ..., Carro E (2018) Platelet proteomic analysis revealed differential pattern of cytoskeletal-and immune-related proteins at early stages of Alzheimer’s disease. Mol Neurobiol 55:8815–8825

  137. Zamoner A, Pessoa-Pureur R (2017) Intermediate filaments as a target of signaling mechanisms in neurotoxicity. In: Intech (ed) Cytoskeleton - structure, dynamics, function and disease. pp 235–236

  138. Wightman EL (2017) Potential benefits of phytochemicals against Alzheimer’s disease. Proc Nutr Soc 76(2):106–112

    Article  PubMed  Google Scholar 

  139. Walsh S, Merrick R, Milne R, Brayne C (2021) Aducanumab for Alzheimer’s disease? BMJ 374

  140. Bhat BA, Almilaibary A, Mir RA, Aljarallah BM, Mir WR, Ahmad F, Mir MA (2022) Natural therapeutics in aid of treating alzheimer’s disease: a green gateway toward ending quest for treating neurological disorders. Front Neurosci 16:884345

    Article  PubMed  PubMed Central  Google Scholar 

  141. Kaur N, Kaur S, Saini M, Dhiman M, Mantha AK (2020) Phytochemical ginkgolide b protects cultured neuroblastoma sh-sy5y cells against aβ (25–35) induced oxidative stress responses by maintaining the mitochondrial integrity. Rasayan J Chem 13(1):306–321

    Article  Google Scholar 

  142. Kaur N, Sarkar B, Gill I, Kaur S, Mittal S, Dhiman M, Mantha AK (2016) Indian herbs and their therapeutic potential against Alzheimer’s disease: what makes them special? In: Neuroprotective Efects of Phytochemicals in Neurological Disorders, Willey Blackwell, Canada, 121:79–112

  143. Kaur N, Sarkar B, Gill I, Kaur S, Mittal S, Dhiman M, Mantha AK (2017) Indian herbs and their therapeutic potential against Alzheimer's disease and other neurological disorders. In: Farooqui, T, Farooqui, A, (eds) Neuroprotective effects of phytochemicals in neurological disorders. New Jersey, United States: John Wiley & Sons, Ltd, pp 79–112

  144. Kaur S, Dhiman M, Mantha AK (2018) Ferulic Acid: a natural antioxidant with application towards neuroprotection against Alzheimer’s disease. Functional Food and Human Health,  Springer, Singapore, pp. 575–586

  145. Kaur S, Verma H, Kaur S, Singh S, Mantha AK, Dhiman M (2022) Herbal remedies for improving cancer treatment through modulation of redox balance. In: Chakraborti S (ed) Handbook of oxidative stress in cancer: therapeutic aspects. Springer, Singapore

    Google Scholar 

  146. Mannangatti P, Naidu KN (2016) Indian herbs for the treatment of neurodegenerative disease. Adv Neurobiol 12:323–336

    Article  PubMed  Google Scholar 

  147. Sánchez-Martínez JD, Valdés A, Gallego R, Suárez-Montenegro ZJ, Alarcón M, Ibañez E, ..., Cifuentes A (2022) Blood–brain barrier permeability study of potential neuroprotective compounds recovered from plants and agri-food by-products. Front Nutr 9:924596

  148. Jayaprakasam B, Padmanabhan K, Nair MG (2010) Withanamides in Withania somnifera fruit protect PC-12 cells from β-amyloid responsible for Alzheimer’s disease. Phytother Res 24(6):859–863

    Article  CAS  PubMed  Google Scholar 

  149. Jayaprakasam B, Strasburg GA, Nair MG (2004) Potent lipid peroxidation inhibitors from Withania somnifera fruits. Tetrahedron 60(13):3109–3121

    Article  CAS  Google Scholar 

  150. Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K (2008) Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol 120(1):112–117

    Article  PubMed  Google Scholar 

  151. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G (2010) Nootropic activity of Celastrus paniculatus seed. Pharm Biol 48(3):324–327

    Article  CAS  PubMed  Google Scholar 

  152. Godkar P, Gordon RK, Ravindran A, Doctor BP (2003) Celastrus paniculatus seed water soluble extracts protect cultured rat forebrain neuronal cells from hydrogen peroxide-induced oxidative injury. Fitoterapia 74(7–8):658–669

    Article  PubMed  Google Scholar 

  153. Rocha MDD, Viegas FP, Campos HC, Nicastro PC, Fossaluzza PC, Fraga CA, Viegas C Jr (2011) The role of natural products in the discovery of new drug candidates for the treatment of neurodegenerative disorders II: Alzheimer’s disease. CNS Neurol Disord Drug Targets 10(2):251–270

    Article  PubMed  Google Scholar 

  154. Rahman MA, Rahman MH, Biswas P, Hossain MS, Islam R, Hannan MA, Rhim H (2020) Potential therapeutic role of phytochemicals to mitigate mitochondrial dysfunctions in Alzheimer’s disease. Antioxidants 10(1):23

    Article  PubMed  PubMed Central  Google Scholar 

  155. Rehman S, Ali Ashfaq U, Sufyan M, Shahid I, Ijaz B, Hussain M (2022) The insight of in silico and in vitro evaluation of beta vulgaris phytochemicals against Alzheimer’s disease targeting acetylcholinesterase. PLoS ONE 17(3):e0264074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Mohammadipour A (2022) A focus on natural products for preventing and cure of mitochondrial dysfunction in Parkinson’s disease. Metab Brain Dis 37(4):889–900

  157. Kagias K, Nehammer C, Pocock R (2012) Neuronal responses to physiological stress. Front Genet 3:222

    Article  PubMed  PubMed Central  Google Scholar 

  158. Koch JC, Bitow F, Haack J, d’Hedouville Z, Zhang JN, Tönges L, Lingor P (2015) Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons. Cell Death Dis 6(7):e1811–e1811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Sone D, Shigemoto Y, Ogawa M, Maikusa N, Okita K, Takano H, Matsuda H (2020) Association between neurite metrics and tau/inflammatory pathology in Alzheimer’s disease. Alzheimer’s Dement 12(1):e12125

    Google Scholar 

  160. Sharoar MG, Palko S, Ge Y, Saido TC, Yan R (2021) Accumulation of saposin in dystrophic neurites is linked to impaired lysosomal functions in Alzheimer’s disease brains. Mol Neurodegener 16(1):1–17

    Article  Google Scholar 

  161. Knobloch M, Mansuy IM (2008) Dendritic spine loss and synaptic alterations in Alzheimer’s disease. Mol Neurobiol 37:73–82

    Article  CAS  PubMed  Google Scholar 

  162. Monserrat Hernández-Hernández E, Serrano-García C, Antonio Vázquez-Roque R, Díaz A, Monroy E, Rodríguez-Moreno A, Flores G (2016) Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats. Synapse 70(5):206–217

    Article  PubMed  Google Scholar 

  163. Bruder JL, Hsieh TC, Lerea KM, Olson SC, Wu JM (2001) Induced cytoskeletal changes in bovine pulmonary artery endothelial cells by resveratrol and the accompanying modified responses to arterial shear stress. BMC Cell Biol 2(1):1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Zhu CW, Grossman H, Neugroschl J, Parker S, Burden A, Luo X, Sano M (2018) A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer’s disease: a pilot study. Alzheimer’s Dement (New York, N. Y.) 4:609–616

    Article  Google Scholar 

  165. Vidal B, Vázquez-Roque RA, Gnecco D, Enríquez RG, Floran B, Díaz A, Flores G (2017) Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats. Synapse 71(3):e21952

    Article  Google Scholar 

  166. Sarkar B, Dhiman M, Mittal S, Mantha AK (2017) Curcumin revitalizes Amyloid beta (25–35)-induced and organophosphate pesticides pestered neurotoxicity in SH-SY5Y and IMR-32 cells via activation of APE1 and Nrf2. Metab Brain Dis 32:2045–2061

  167. Kaur H, Patro I, Tikoo K, Sandhir R (2015B) Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy. Neurochem Int 89:40–50

    Article  CAS  PubMed  Google Scholar 

  168. Liu C, Chan CB, Ye K (2016) 7, 8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener 5(1):1–9

    Article  Google Scholar 

  169. Huang WL, Ma YX, Fan YB, Lai SM, Liu HQ, Liu J, Tian SM (2017) Extract of Ginkgo biloba promotes neuronal regeneration in the hippocampus after exposure to acrylamide. Neural Regen Res 12(8):1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Gill I, Kaur S, Kaur N, Dhiman M, Mantha AK (2017) Phytochemical ginkgolide B attenuates amyloid-β 1–42 induced oxidative damage and altered cellular responses in human neuroblastoma SH-SY5Y cells. J Alzheimers Dis 60(s1):S25–S40

    Article  CAS  PubMed  Google Scholar 

  171. Kaur N, Dhiman M, Perez-Polo JR, Mantha AK (2015A) Ginkgolide B revamps neuroprotective role of apurinic/apyrimidinic endonuclease 1 and mitochondrial oxidative phosphorylation against Aβ25–35-induced neurotoxicity in human neuroblastoma cells. J Neurosci Res 93(6):938–947

    Article  CAS  PubMed  Google Scholar 

  172. Zheng PD, Mungur R, Zhou HJ, Hassan M, Jiang SN, Zheng JS (2018) Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro. Neural Regen Res 13(7):1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Jaafaru MS, Nordin N, Shaari K, Rosli R, Abdull Razis AF (2018) Isothiocyanate from Moringa oleifera seeds mitigates hydrogen peroxide-induced cytotoxicity and preserved morphological features of human neuronal cells. PLoS ONE 13(5):e0196403

    Article  PubMed  PubMed Central  Google Scholar 

  174. Thapliyal S, Singh T, Handu S, Bisht M, Kumari P, Arya P, ..., Gandham R (2021) A review on potential footprints of ferulic acid for treatment of neurological disorders. Neurochem Res 46(5):1043–1057

  175. Huang H, Hong Q, Tan HL, Xiao CR, Gao Y (2016) Ferulic acid prevents LPS-induced up-regulation of PDE4B and stimulates the cAMP/CREB signaling pathway in PC12 cells. Acta Pharmacol Sin 37(12):1543–1554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Hiruma H, Katakura T, Takahashi S, Ichikawa T, Kawakami T (2003) Glutamate and amyloid β-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J Neurosci 23(26):8967–8977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Chiang NN, Lin TH, Teng YS, Sun YC, Chang KH, Lin CY, Lee-Chen GJ (2021) Flavones 7, 8-DHF, quercetin, and apigenin against tau toxicity via activation of TRKB signaling in ΔK280 TauRD-DsRed SH-SY5Y Cells. Frontiers in Aging Neuroscience 13:758895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Sajad M, Kumar R, Thakur SC (2022) History in perspective: the prime pathological players and role of phytochemicals in Alzheimer’s disease. IBRO Neurosci Rep 12:377–389

  179. Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T (2007) A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25–35. Behav Brain Res 180(2):139–145

    Article  CAS  PubMed  Google Scholar 

  180. Musi N, Valentine JM, Sickora KR, Baeuerle E, Thompson CS, Shen Q, Orr ME (2018) Tau protein aggregation is associated with cellular senescence in the brain. Aging Cell 17(6):e12840

    Article  PubMed  PubMed Central  Google Scholar 

  181. Gonzales MM, Krishnamurthy S, Garbarino V, Daeihagh AS, Gillispie GJ, Deep G, ..., Orr ME (2021) A geroscience motivated approach to treat Alzheimer’s disease: senolytics move to clinical trials. Mech Ageing Devel 200:111589

  182. Zhang P, Kishimoto Y, Grammatikakis I, Gottimukkala K, Cutler RG, Zhang S, ..., Mattson MP (2019) Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model. Nat Neurosci 22(5):719–728

  183. Kataria H, Wadhwa R, Kaul SC, Kaur G (2013) Withania somnifera water extract as a potential candidate for differentiation-based therapy of human neuroblastomas. PLoSOne 8(1):e55316

    Article  ADS  CAS  Google Scholar 

  184. Kuboyama T, Tohda C, Komatsu K (2005) Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol 144(7):961–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Akama KT, McEwen BS (2003) Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway. J Neurosci 23(6):2333–2339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Dominguez R, Jalali C, de Lacalle S (2004) Morphological effects of estrogen on cholinergic neurons in vitro involves activation of extracellular signal-regulated kinases. J Neurosci 24(4):982–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K (2002) Axon-or dendrite-predominant outgrowth induced by constituents from Ashwagandha. NeuroReport 13(14):1715–1720

    Article  CAS  PubMed  Google Scholar 

  188. Yokomaku D, Numakawa T, Numakawa Y, Suzuki S, Matsumoto T, Adachi N, ...,. Hatanaka H (2003) Estrogen enhances depolarization-induced glutamate release through activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase in cultured hippocampal neurons. Mol Endocrinol 17(5):831–844

  189. Tohda C, Kuboyama T, Komatsu K (2000) Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells. NeuroReport 11(9):1981–1985

    Article  CAS  PubMed  Google Scholar 

  190. Shao CY, Mirra SS, Sait HB, Sacktor TC, Sigurdsson EM (2011) Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer’s disease. Acta Neuropathol 122:285–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Ghosh A, Giese KP (2015) Calcium/calmodulin-dependent kinase II and Alzheimer’s disease. Mol Brain 8(1):1–7

    Article  CAS  Google Scholar 

  192. Shang YY, Ma YJ, Zhang L, Wang LJ, Wu XF, Liu XP (2018) Flavonoids extracted from leaves of Diospyros kaki regulates RhoA activity to rescue synapse loss and reverse memory impairment in APP/PS1 mice. NeuroReport 29(7):564–569

    Article  CAS  PubMed  Google Scholar 

  193. Wang Y, Wang L, Wu J, Cai J (2006) The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats. Br J Pharmacol 148(2):147–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Shi M, Chu F, Zhu F, Zhu J (2022) Impact of anti-amyloid-β monoclonal antibodies on the pathology and clinical profile of Alzheimer’s disease: a focus on aducanumab and lecanemab. Front Aging Neurosci 14:870517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Libro R, Giacoppo S, Soundara Rajan T, Bramanti P, Mazzon E (2016) Natural phytochemicals in the treatment and prevention of dementia: an overview. Molecules (Basel, Switzerland) 21(4):518

    Article  PubMed  Google Scholar 

  196. Velmurugan BK, Rathinasamy B, Lohanathan BP, Thiyagarajan V, Weng CF (2018) Neuroprotective role of phytochemicals. Molecules (Basel, Switzerland) 23(10):2485

    Article  PubMed  Google Scholar 

  197. Kim J, Lee HJ, Lee KW (2010) Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem 112(6):1415–1430

    Article  CAS  PubMed  Google Scholar 

  198. Leisher S, Bohorquez A, Gay M, Garcia V, Jones R, Baldaranov D, Rafii MS (2023) Amyloid-lowering monoclonal antibodies for the treatment of early Alzheimer’s disease. CNS Drugs 37(8):671–677

  199. Moore KB, Hung TJ, Fortin JS (2023) Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer’s disease and related tauopathies. Drug Discovery Today 28(3):103487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Grossberg GT (2003) Cholinesterase inhibitors for the treatment of Alzheimer’s disease: getting on and staying on. Curr Ther Res Clin Exp 64(4):216–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Liao Y, Mai X, Wu X, Hu X, Luo X, Zhang G (2022) Exploring the inhibition of quercetin on acetylcholinesterase by multispectroscopic and in silico approaches and evaluation of its neuroprotective effects on PC12 cells. Molecules (Basel, Switzerland) 27(22):7971

    Article  CAS  PubMed  Google Scholar 

  202. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M, da Rosa MM, Rubin MA, Chitolina Schetinger MR, Morsch VM (2009) Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol 610(1–3):42–48

    Article  CAS  PubMed  Google Scholar 

  203. Paladugu L, Gharaibeh A, Kolli N, Learman C, Hall TC, Li L, ..., Dunbar GL (2021) Liraglutide has anti-inflammatory and anti-amyloid properties in streptozotocin-induced and 5xFAD mouse models of Alzheimer’s disease. Int J Mol Sci 22(2):860

  204. Duarte AI, Candeias E, Alves IN, Mena D, Silva DF, Machado NJ, Campos EJ, Santos MS, Oliveira CR, Moreira PI (2020) Liraglutide Protects Against Brain Amyloid-β1-42 Accumulation in female mice with early Alzheimer’s disease-like pathology by partially rescuing oxidative/nitrosative stress and inflammation. Int J Mol Sci 21(5):1746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Nadeem MS, Kazmi I, Ullah I, Muhammad K, Anwar F (2021) Allicin, an antioxidant and neuroprotective agent, ameliorates cognitive impairment. Antioxidants (Basel, Switzerland) 11(1):87

    PubMed  Google Scholar 

  206. Tiwari V, Chopra K (2012) Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents cognitive deficits in rats postnatally exposed to ethanol. Psychopharmacology 224:519–535

    Article  CAS  PubMed  Google Scholar 

  207. Moghimi-Khorasgani A, Homayouni Moghadam F, Nasr-Esfahani MH (2023) Ferulic Acid reduces amyloid beta mediated neuroinflammation through modulation of Nurr1 expression in microglial cells. PLoS ONE 18(8):e0290249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Sun M, Sheng Y, Zhu Y (2021) Ginkgolide B alleviates the inflammatory response and attenuates the activation of LPS-induced BV2 cells in vitro and in vivo. Exp Ther Med 21(6):586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Aqil F, Munagala R, Jeyabalan J, Vadhanam MV (2013) Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett 334(1):133–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Das KC, Das CK (2002) Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochem Biophys Res Commun 295(1):62–66

    Article  CAS  PubMed  Google Scholar 

  211. Ono K, Hasegawa K, Naiki H, Yamada M (2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer’s β-amyloid fibrils in vitro. J Neurosci Res 75(6):742–750

    Article  CAS  PubMed  Google Scholar 

  212. Ramsewak RS, DeWitt DL, Nair MG (2000) Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine 7(4):303–308

    Article  CAS  PubMed  Google Scholar 

  213. Scapagnini G, Sonya V, Nader AG, Calogero C, Zella D, Fabio G (2011) Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol Neurobiol 44:192–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Sreejayan XX, Rao MNA (1997) Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol 49(1):105–107

    Article  CAS  PubMed  Google Scholar 

  215. Davinelli S, Sapere N, Zella D, Bracale R, Intrieri M, Scapagnini G (2012) Pleiotropic protective effects of phytochemicals in Alzheimer’s disease. Oxidative Med Cell Longev 2012:1–11

    Article  Google Scholar 

  216. Sharma RA, Gescher AJ, Steward WP (2005) Curcumin: the story so far. Eur J Cancer 41(13):1955–1968

    Article  CAS  PubMed  Google Scholar 

  217. Tønnesen HH, Másson M, Loftsson T (2002) Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int J Pharm 244(1–2):127–135

    Article  PubMed  Google Scholar 

  218. Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, ..., Bradshaw PC (2011) Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer's amyloid-induced mitochondrial dysfunction. J Alzheimer's Dis 26(3):507–521

  219. Lin LC, Wang MN, Tseng TY, Sung, Tsai TH (2007) Pharmacokinetics of (−)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J Agric Food Chem 55(4):1517–1524

    Article  CAS  PubMed  Google Scholar 

  220. Wang JH, Cheng J, Li CR, Ye M, Ma Z, Cai F (2011) Modulation of Ca2+ signals by epigallocatechin-3-gallate (EGCG) in cultured rat hippocampal neurons. Int J Mol Sci 12(1):742–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Charytoniuk T, Drygalski K, Konstantynowicz-Nowicka K, Berk K, Chabowski A (2017) Alternative treatment methods attenuate the development of NAFLD: a review of resveratrol molecular mechanisms and clinical trials. Nutrition 34:108–117

    Article  CAS  PubMed  Google Scholar 

  222. Krasnow MN, Murphy TM (2004) Polyphenol glucosylating activity in cell suspensions of grape (Vitis vinifera). J Agric Food Chem 52(11):3467–3472

    Article  CAS  PubMed  Google Scholar 

  223. Chen M, Du ZY, Zheng X, Li DL, Zhou RP, Zhang K (2018) Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease. Neural Regen Res 13(4):742–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y, ..., Kumar DS (2012) Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer's disease. PLoS One 7(3):e32616

  225. Hagl S, Kocher A, Schiborr C, Kolesova N, Frank J, Eckert GP (2015) Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice–Impact on bioavailability. Neurochem Int 89:234–242

    Article  CAS  PubMed  Google Scholar 

  226. Nahar PP, Slitt AL, Seeram NP (2015) Anti-inflammatory effects of novel standardized solid lipid curcumin formulations. J Med Food 18(7):786–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, Soni MG (2011) Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food Chem Toxicol 49(8):1834–1842

    Article  CAS  PubMed  Google Scholar 

  228. Sandhir R, Yadav A, Mehrotra A, Sunkaria A, Singh A, Sharma S (2014) Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. NeuroMol Med 16:106–118

    Article  CAS  Google Scholar 

  229. Saini S, Sharma T, Jain A, Kaur H, Katare OP, Singh B (2021) Systematically designed chitosan-coated solid lipid nanoparticles of ferulic acid for effective management of Alzheimer’s disease: a preclinical evidence. Colloids Surf B 205:111838–111850

    Article  CAS  Google Scholar 

  230. Jordão JF, Ayala-Grosso CA, Markham K, Huang Y, Chopra R, McLaurin J, Hynynen K, Aubert I (2010) Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer’s disease. PLoS ONE 5(5):e10549

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  231. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345

    Article  CAS  PubMed  Google Scholar 

  232. He J, Ren W, Wang W, Han W, Jiang L, Zhang D, Guo M (2022) Exosomal targeting and its potential clinical application. Drug Deliv Transl Res 12(10):2385–2402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Gothwal A, Kumar H, Nakhate KT, Ajazuddin, Dutta A, Borah A, Gupta U (2019) Lactoferrin coupled lower generation PAMAM dendrimers for brain targeted delivery of memantine in aluminum-chloride-induced Alzheimer’s disease in mice. Bioconjug Chem 30(10):2573–2583

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

H.V. and S.K., and P.G. acknowledges financial support in the form of a junior research fellowship (JRF) from the University Grants Commission (UGC) and Dept. of Biotechnology (DBT), Govt. of India, New Delhi, India, respectively. Because of the limited focus of the article, many relevant and appropriate references could not be included, for which the authors apologize.

Funding

A.K.M and M.D. thankfully acknowledges financial support in the form of Core Research Grant (CRG/2021/002524) from SERB, DST, Govt. of India, New Delhi, India.

Author information

Author notes

  1. Harkomal Verma and Sharanjot Kaur contributed equally to this work.

Authors and Affiliations

  1. Department of Zoology, School of Basic Sciences, Central University of Punjab, Village Ghudda, VPO – Ghudda, Bathinda, 151 401, Punjab, India

    Harkomal Verma, Prabhakar Gangwar & Anil Kumar Mantha

  2. Department of Microbiology, School of Basic Sciences, Central University of Punjab, Village Ghudda, Bathinda, Punjab, India

    Sharanjot Kaur, Sukhchain Kaur & Monisha Dhiman

Authors
  1. Harkomal Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharanjot Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sukhchain Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prabhakar Gangwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Monisha Dhiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anil Kumar Mantha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AKM and MD conceived the idea and outline of the manuscript. HV and SK (both of them contributed equally) performed literature review, wrote the manuscript, and made the figures and tables along with PG and SK. All authors have read the manuscript and agreed to the final draft of the manuscript.

Corresponding author

Correspondence to Anil Kumar Mantha.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verma, H., Kaur, S., Kaur, S. et al. Role of Cytoskeletal Elements in Regulation of Synaptic Functions: Implications Toward Alzheimer’s Disease and Phytochemicals-Based Interventions. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04053-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04053-3

Keywords

Search

Navigation