Neuronal response in Alzheimer’s and Parkinson’s disease: the effect of toxic proteins on intracellular pathways (original) (raw)
Uversky VN. Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: which way to go? Cell Mol Life Sci. 2003;60(9):1852–71. ArticleCASPubMed Google Scholar
Stefani M, Rigacci S. Protein folding and aggregation into amyloid: the interference by natural phenolic compounds. Int J Mol Sci. 2013;14(6):12411–57. ArticlePubMed CentralPubMedCAS Google Scholar
Kakizuka A. Protein precipitation: a common etiology in neuro-degenerative disorders? Trends Genet. 1998;14(10):396–402. ArticleCASPubMed Google Scholar
Karpinar DP, Balija MB, Kugler S, Opazo F, Rezaei-Ghaleh N, Wender N, Kim HY, Taschenberger G, Falkenburger BH, Heise H, et al. Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson’s disease models. EMBO J. 2009;28(20):3256–68. ArticlePubMed CentralCASPubMed Google Scholar
Borgia MB, Borgia A, Best RB, Steward A, Nettels D, Wunderlich B, Schuler B, Clarke J. Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins. Nature. 2011;474(7353):662–5. ArticlePubMed CentralCASPubMed Google Scholar
Stefani M. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta. 2004;1739(1):5–25. ArticleCASPubMed Google Scholar
Winklhofer KF, Tatzelt J, Haass C. The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J. 2008;27(2):336–49. ArticlePubMed CentralCASPubMed Google Scholar
Abelein A, Bolognesi B, Dobson CM, Graslund A, Lendel C. Hydrophobicity and conformational change as mechanistic determinants for nonspecific modulators of amyloid beta self-assembly. Biochemistry. 2012;51(1):126–37. ArticleCASPubMed Google Scholar
Blokhuis AM, Groen EJ, Koppers M, van den Berg LH, Pasterkamp RJ. Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol. 2013;125(6):777–94. ArticlePubMed CentralCASPubMed Google Scholar
Selkoe DJ. Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann N Y Acad Sci. 2000;924:17–25. ArticleCASPubMed Google Scholar
Kumar S, Wirths O, Theil S, Gerth J, Bayer TA, Walter J. Early intraneuronal accumulation and increased aggregation of phosphorylated Abeta in a mouse model of Alzheimer’s disease. Acta Neuropathol. 2013;125(5):699–709. ArticleCASPubMed Google Scholar
Lansbury PT Jr. Structural neurology: are seeds at the root of neuronal degeneration? Neuron. 1997;19(6):1151–4. ArticleCASPubMed Google Scholar
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26(40):10129–40. ArticleCASPubMed Google Scholar
Storey E, Cappai R. The amyloid precursor protein of Alzheimer’s disease and the Abeta peptide. Neuropathol Appl Neurobiol. 1999;25(2):81–97. ArticleCASPubMed Google Scholar
Nunan J, Small DH. Regulation of APP cleavage by alpha-, beta- and gamma- secretases. FEBS Lett. 2000;483(1):6–10. ArticleCASPubMed Google Scholar
Ho A, Sudhof TC. Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proc Natl Acad Sci USA. 2004;101(8):2548–53. ArticlePubMed CentralCASPubMed Google Scholar
Schubert D, Klar A, Park M, Dargusch R, Fischer WH. F-spondin promotes nerve precursor differentiation. J Neurochem. 2006;96(2):444–53. ArticleCASPubMed Google Scholar
Kamal A, Stokin GB, Yang Z, Xia CH, Goldstein LS. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron. 2000;28(2):449–59. ArticleCASPubMed Google Scholar
Gouras GK, Xu H, Jovanovic JN, Buxbaum JD, Wang R, Greengard P, Relkin NR, Gandy S. Generation and regulation of beta-amyloid peptide variants by neurons. J Neurochem. 1998;71(5):1920–5. ArticleCASPubMed Google Scholar
Schneider A, Rajendran L, Honsho M, Gralle M, Donnert G, Wouters F, Hell SW, Simons M. Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons. J Neurosci. 2008;28(11):2874–82. ArticleCASPubMed Google Scholar
Sarajarvi T, Tuusa JT, Haapasalo A, Lackman JJ, Sormunen R, Helisalmi S, Roehr JT, Parrado AR, Makinen P, Bertram L, et al. Cysteine 27 variant of the delta-opioid receptor affects amyloid precursor protein processing through altered endocytic trafficking. Mol Cell Biol. 2011;31(11):2326–40. ArticlePubMed CentralCASPubMed Google Scholar
Wang X, Huang T, Bu G, Xu H. Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegenr. 2014;9(31):1–9. Google Scholar
Olah J, Vincze O, Virok D, Simon D, Bozso Z, Tokesi N, Horvath I, Hlavanda E, Kovacs J, Magyar A, et al. Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J Biol Chem. 2011;286(39):34088–100. ArticlePubMed CentralCASPubMed Google Scholar
Howlett DR, Simmons DL, Dingwall C, Christie G. In search of an enzyme: the beta-secretase of Alzheimer’s disease is an aspartic proteinase. Trends Neurosci. 2000;23(11):565–70. ArticleCASPubMed Google Scholar
Takami M, Nagashima Y, Sano Y, Ishihara S, Morishima-Kawashima M, Funamoto S, Ihara Y. gamma-Secretase: successive tripeptide and tetrapeptide release from the transmembrane domain of beta-carboxyl terminal fragment. J Neurosci. 2009;29(41):13042–52. ArticleCASPubMed Google Scholar
Wiley JC, Hudson M, Kanning KC, Schecterson LC, Bothwell M. Familial Alzheimer’s disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment. J Neurochem. 2005;94(5):1189–201. ArticleCASPubMed Google Scholar
Davis-Salinas J, Saporito-Irwin SM, Cotman CW, Van Nostrand WE. Amyloid beta-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells. J Neurochem. 1995;65(2):931–4. ArticleCASPubMed Google Scholar
Majd S, Rastegar K, Zarifkar A, Takhshid MA. Fibrillar beta-amyloid (Abeta) (1-42) elevates extracellular Abeta in cultured hippocampal neurons of adult rats. Brain Res. 2007;1185:321–7. ArticleCASPubMed Google Scholar
Casas C, Sergeant N, Itier JM, Blanchard V, Wirths O, van der Kolk N, Vingtdeux V, van de Steeg E, Ret G, Canton T, et al. Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. Am J Pathol. 2004;165(4):1289–300. ArticlePubMed CentralCASPubMed Google Scholar
Yamamoto K, Shimada H, Koh H, Ataka S, Miki T. Serum levels of albumin-amyloid beta complexes are decreased in Alzheimer’s disease. Geriatr Gerontol Int. 2014;14(3):716–23. ArticlePubMed Google Scholar
Sunde M, Blake CC. From the globular to the fibrous state: protein structure and structural conversion in amyloid formation. Q Rev Biophys. 1998;31:1–39. ArticleCASPubMed Google Scholar
Benzinger TL, Gregory DM, Burkoth TS, Miller-Auer H, Lynn DG, Botto RE, Meredith SC. Propagating structure of Alzheimer’s beta-amyloid(10-35) is parallel beta-sheet with residues in exact register. Proc Natl Acad Sci USA. 1998;95:13407–12. ArticlePubMed CentralCASPubMed Google Scholar
Tycko R. Insights into the amyloid folding problem from solid-state NMR. Biochemistry. 2003;42:3151–9. ArticleCASPubMed Google Scholar
Torok M, Milton S, Kayed R, Wu P, McIntire T, Glabe CG, Langen R. Structural and dynamic features of Alzheimer’s Aβ peptide in amyloid fibrils studied by site-directed spin labeling. J Biol Chem. 2002;277:40810–5. ArticlePubMedCAS Google Scholar
Yanagisawa K. Role of gangliosides in Alzheimer’s disease. Biochim Biophys Acta. 2002;1768:1943–51. ArticleCAS Google Scholar
De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL. Abeta oligomers induce neuronal oxidative stress through an _N_-methyl-d-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem. 2002;282:11590–601. ArticleCAS Google Scholar
Laferla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci. 2007;8:499–509. ArticleCASPubMed Google Scholar
Almeida CG, Takahashi RH, Gouras GK. Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci. 2006;26:4277–88. ArticleCASPubMed Google Scholar
Huse JT, Doms RW. Closing in on the amyloid cascade: recent insights into the cell biology of Alzheimer’s disease. Mol Neurobiol. 2000;22(1–3):81–98. CASPubMed Google Scholar
Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J. Therapeutic approaches to Alzheimer’s disease. Brain. 2006;129(Pt 11):2840–55. ArticlePubMed Google Scholar
Wertkin AM, Turner RS, Pleasure SJ, Golde TE, Younkin SG, Trojanowski JQ, Lee VM. Human neurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular beta- amyloid or A4 peptides. Proc Natl Acad Sci USA. 1993;90(20):9513–7. ArticlePubMed CentralCASPubMed Google Scholar
Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol. 2002;161(5):1869–79. ArticlePubMed CentralCASPubMed Google Scholar
Alvira-Botero X, Perez-Gonzalez R, Spuch C, Vargas T, Antequera D, Garzon M, Bermejo-Pareja F, Carro E. Megalin interacts with APP and the intracellular adapter protein FE65 in neurons. Mol Cell Neurosci. 2010;45(3):306–15. ArticleCASPubMed Google Scholar
Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron. 2007;56(1):66–78. ArticlePubMed CentralCASPubMed Google Scholar
Spuch C, Ortolano S, Navarro C. LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer’s disease. Front Physiol. 2012;3:269. ArticlePubMed CentralPubMedCAS Google Scholar
Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, et al. RAGE-mediated signalling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. Proc Natl Acad Sci USA. 2009;106(47):20021–6. ArticlePubMed CentralCASPubMed Google Scholar
Cook DG, Forman MS, Sung JC, Leight S, Kolson DL, Iwatsubo T, Lee VM, Doms RW. Alzheimer’s Abeta(1-42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells. Nat Med. 1997;3(9):1021–3. ArticleCASPubMed Google Scholar
Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P, Xu H. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proc Natl Acad Sci USA. 1999;96(2):742–7. ArticlePubMed CentralCASPubMed Google Scholar
Sudoh S, Kawamura Y, Sato S, Wang R, Saido TC, Oyama F, Sakaki Y, Komano H, Yanagisawa K. Presenilin 1 mutations linked to familial Alzheimer’s disease increase the intracellular levels of amyloid beta-protein 1-42 and its N-terminally truncated variant(s) which are generated at distinct sites. J Neurochem. 1998;71(4):1535–43. ArticleCASPubMed Google Scholar
UamekKozio M, Furmaga-Jaboska W, Januszewski S, Brzozowska J, Scilewska M, Jaboski M, Pluta R. Neuronal autophagy: self-eating or self-cannibalism in Alzheimer’s disease. Neurochem Res. 2013;38:1769–73. ArticleCAS Google Scholar
Son SM, Jung ES, Shin HJ, Byun J, Mook-Jung I. Aβ-induced formation of autophagosomes is mediated by RAGECaMKK β-AMPK signaling. Neurobiol Aging. 2012;33:1006.e11–23. ArticleCAS Google Scholar
Bayer TA, Wirths O, Majtenyi K, Hartmann T, Multhaup G, Beyreuther K, Czech C. Key factors in Alzheimer’s disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol. 2001;11(1):1–11. ArticleCASPubMed Google Scholar
Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW. Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA. 1993;90(17):7951–5. ArticlePubMed CentralCASPubMed Google Scholar
Versen LL, Mortishire-Smith RJ, Pollack SJ, Shearman MS. The toxicity in vitro of beta-amyloid protein. Biochem J. 1995;311(Pt 1):1–16. Article Google Scholar
Parihar MS, Hemnani T. Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci. 2004;11(5):456–67. ArticleCASPubMed Google Scholar
Hoshi M, Takashima A, Noguchi K, Murayama M, Sato M, Kondo S, Saitoh Y, Ishiguro K, Hoshino T, Imahori K. Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in brain. Proc Natl Acad Sci USA. 1996;93(7):2719–23. ArticlePubMed CentralCASPubMed Google Scholar
Jope RS, Johnson GV. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci. 2004;29(2):95–102. ArticleCASPubMed Google Scholar
Gomez-Sintes R, Hernandez F, Lucas JJ, Avila J. GSK-3 mouse models to study neuronal apoptosis and neurodegeneration. Front Mol Neurosci. 2011;4:45. ArticlePubMed CentralCASPubMed Google Scholar
Pei JJ, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. J Neuropathol Exp Neurol. 1999;58(9):1010–9. ArticleCASPubMed Google Scholar
Yamaguchi H, Ishiguro K, Uchida T, Takashima A, Lemere CA, Imahori K. Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II. Acta Neuropathol. 1996;92(3):232–41. ArticleCASPubMed Google Scholar
Kettunen P, Larsson S, Holmgren S, Olsson S, Minthon L, Zetterberg H, Blennow K, Nilsson S, Sjölander A. Genetic variants of GSK3B are associated with biomarkers for Alzheimer’s disease and cognitive function. J Alzheimers Dis. 2015;44(4):1313–22. CASPubMed Google Scholar
Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, Lasrado R, Vandezande K, Laenen I, Boon T, et al. Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. J Biol Chem. 2000;275(52):41340–9. ArticleCASPubMed Google Scholar
Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J. 2001;20(1–2):27–39. ArticlePubMed CentralCASPubMed Google Scholar
Hansen T, Rehfeld JF, Nielsen FC. GSK-3beta reduces cAMP-induced cholecystokinin gene expression by inhibiting CREB binding. NeuroReport. 2004;15(5):841–5. ArticleCASPubMed Google Scholar
Jope RS, Yuskaitis CJ, Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res. 2007;32(4–5):577–95. ArticlePubMed CentralCASPubMed Google Scholar
Townsend M, Mehta T, Selkoe DJ. Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J Biol Chem. 2007;282(46):33305–12. ArticleCASPubMed Google Scholar
Magdesian MH, Carvalho MM, Mendes FA, Saraiva LM, Juliano MA, Juliano L, Garcia-Abreu J, Ferreira ST. Amyloid-beta binds to the extracellular cysteine- rich domain of Frizzled and inhibits Wnt/beta-catenin signaling. J Biol Chem. 2008;283(14):9359–68. ArticlePubMed CentralCASPubMed Google Scholar
Yan J, Liu XH, Han MZ, Wang YM, Sun XL, Yu N, Li T, Su B, Chen ZY. Blockage of GSK3β-mediated Drp1 phosphorylation provides neuroprotection in neuronal and mouse models of Alzheimer’s disease. Neurobiol Aging. 2015;36(1):211–27. ArticleCASPubMed Google Scholar
Imahori K, Uchida T. Physiology and pathology of tau protein kinases in relation to Alzheimer’s disease. J Biochem. 1997;121(2):179–88. CASPubMed Google Scholar
Echeverria V, Ducatenzeiler A, Dowd E, Janne J, Grant SM, Szyf M, Wandosell F, Avila J, Grimm H, Dunnett SB, et al. Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons. Neuroscience. 2004;129(3):583–92. ArticleCASPubMed Google Scholar
Espana J, Gimenez-Llort L, Valero J, Minano A, Rabano A, Rodriguez-Alvarez J, LaFerla FM, Saura CA. Intraneuronal beta-amyloid accumulation in the amygdala enhances fear and anxiety in Alzheimer’s disease transgenic mice. Biol Psychiatry. 2010;67(6):513–21. ArticleCASPubMed Google Scholar
Trojanowski JQ, Mawal-Dewan M, Schmidt ML, Martin J, Lee VM. Localization of the mitogen activated protein kinase ERK2 in Alzheimer’s disease neurofibrillary tangles and senile plaque neurites. Brain Res. 1993;618(2):333–7. ArticleCASPubMed Google Scholar
Pei JJ, Braak H, An WL, Winblad B, Cowburn RF, Iqbal K, Grundke-Iqbal I. Up- regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer’s disease. Brain Res Mol Brain Res. 2002;109(1–2):45–55. ArticleCASPubMed Google Scholar
Harada T, Morooka T, Ogawa S, Nishida E. ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1. Nat Cell Biol. 2001;3(5):453–9. ArticleCASPubMed Google Scholar
Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44. ArticlePubMed CentralCASPubMed Google Scholar
Pende M, Um SH, Mieulet V, Sticker M, Goss VL, Mestan J, Mueller M, Fumagalli S, Kozma SC, Thomas G. S6K1(−/−)/S6K2(−/−) mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol Cell Biol. 2004;24(8):3112–24. ArticlePubMed CentralCASPubMed Google Scholar
Ferrer I, Blanco R, Carmona M, Puig B, Barrachina M, Gomez C, Ambrosio S. Active, phosphorylation-dependent mitogen-activated protein kinase (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 kinase expression in Parkinson’s disease and Dementia with Lewy bodies. J Neural Transm. 2001;108(12):1383–96. ArticleCASPubMed Google Scholar
Ferrer I, Blanco R, Carmona M, Puig B. Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38 kDa (p38-P), stress- activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaM kinase II) are differentially expressed in tau deposits in neurons and glial cells in tauopathies. J Neural Transm. 2001;108(12):1397–415. ArticleCASPubMed Google Scholar
Kosik KS, Shimura H. Phosphorylated tau and the neurodegenerative foldopathies. Biochim Biophys Acta. 2005;1739(2–3):298–310. ArticleCASPubMed Google Scholar
Lambourne SL, Sellers LA, Bush TG, Choudhury SK, Emson PC, Suh YH, Wilkinson LS. Increased tau phosphorylation on mitogen-activated protein kinase consensus sites and cognitive decline in transgenic models for Alzheimer’s disease and FTDP-17: evidence for distinct molecular processes underlying tau abnormalities. Mol Cell Biol. 2005;25(1):278–93. ArticlePubMed CentralCASPubMed Google Scholar
Mandelkow E, Song YH, Schweers O, Marx A, Mandelkow EM. On the structure of microtubules, tau, and paired helical filaments. Neurobiol Aging. 1995;16(3):347–54. ArticleCASPubMed Google Scholar
Iqbal K, Alonso AC, Gong CX, Khatoon S, Pei JJ, Wang JZ, Grundke-Iqbal I. Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles. J Neural Transm Suppl. 1998;53:169–80. ArticleCASPubMed Google Scholar
Dickson TC, King CE, McCormack GH, Vickers JC. Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer’s disease. Exp Neurol. 1999;156(1):100–10. ArticleCASPubMed Google Scholar
Vickers JC, Dickson TC, Adlard PA, Saunders HL, King CE, McCormack G. The cause of neuronal degeneration in Alzheimer’s disease. Prog Neurobiol. 2000;60(2):139–65. ArticleCASPubMed Google Scholar
Masliah E, Terry RD, DeTeresa RM, Hansen LA. Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease. Neurosci Lett. 1989;103(2):234–9. ArticleCASPubMed Google Scholar
Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer’s disease. J Neurosci. 1996;16(18):5795–811. CASPubMed Google Scholar
Henriques AG, Vieira SI, da Cruz ESEF, da Cruz ESOA. Abeta promotes Alzheimer’s disease-like cytoskeleton abnormalities with consequences to APP processing in neurons. J Neurochem. 2010;113(3):761–71. ArticleCASPubMed Google Scholar
Braak H, Del Tredici K. Alzheimer’s disease: intraneuronal alterations precede insoluble amyloid-beta formation. Neurobiol Aging. 2004;25(6):713–8 (discussion 743–716). ArticlePubMed Google Scholar
Fernandez-Vizarra P, Fernandez AP, Castro-Blanco S, Serrano J, Bentura ML, Martinez-Murillo R, Martinez A, Rodrigo J. Intra- and extracellular Abeta and PHF in clinically evaluated cases of Alzheimer’s disease. Histol Histopathol. 2004;19(3):823–44. CASPubMed Google Scholar
Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, Yen SH, Sahara N, Skipper L, Yager D, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001;293(5534):1487–91. ArticleCASPubMed Google Scholar
Mudher A, Lovestone S. Alzheimer’s disease-do tauists and baptists finally shake hands? Trends Neurosci. 2002;25(1):22–6. ArticleCASPubMed Google Scholar
Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, et al. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signalling: suppression by omega-3 fatty acids and curcumin. J Neurosci. 2009;29(28):9078–89. ArticlePubMed CentralCASPubMed Google Scholar
Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science. 2001;293(5534):1491–5. ArticleCASPubMed Google Scholar
Ishihara T, Zhang B, Higuchi M, Yoshiyama Y, Trojanowski JQ, Lee VM. Age-dependent induction of congophilic neurofibrillary tau inclusions in tau transgenic mice. Am J Pathol. 2001;158(2):555–62. ArticlePubMed CentralCASPubMed Google Scholar
Saunders AM. Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses. J Neuropathol Exp Neurol. 2000;59(9):751–8. CASPubMed Google Scholar
Wisniewski T, Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett. 1992;135(2):235–8. ArticleCASPubMed Google Scholar
Fleming LM, Weisgraber KH, Strittmatter WJ, Troncoso JC, Johnson GV. Differential binding of apolipoprotein E isoforms to tau and other cytoskeletal proteins. Exp Neurol. 1996;138(2):252–60. ArticleCASPubMed Google Scholar
Ly S, Altman R, Petrlova J, Lin Y, Hilt S, Huser T, Laurence TA, Voss JC. Binding of apolipoprotein E inhibits the oligomer growth of amyloid-beta peptide in solution as determined by fluorescence cross-correlation spectroscopy. J Biol Chem. 2013;288(17):11628–35. ArticlePubMed CentralCASPubMed Google Scholar
Smith JD. Apolipoprotein E4: an allele associated with many diseases. Ann Med. 2000;32(2):118–27. ArticleCASPubMed Google Scholar
Ladu MJ, Reardon C, Van Eldik L, Fagan AM, Bu G, Holtzman D, Getz GS. Lipoproteins in the central nervous system. Ann N Y Acad Sci. 2000;903:167–75. ArticleCASPubMed Google Scholar
Carter DB, Dunn E, McKinley DD, Stratman NC, Boyle TP, Kuiper SL, Oostveen JA, Weaver RJ, Boller JA, Gurney ME. Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain. Ann Neurol. 2001;50(4):468–75. ArticleCASPubMed Google Scholar
Cho KH, Durbin DM, Jonas A. Role of individual amino acids of apolipoprotein A-I in the activation of lecithin: cholesterol acyltransferase and in HDL rearrangements. J Lipid Res. 2001;42(3):379–89. CASPubMed Google Scholar
Varadarajan S, Yatin S, Aksenova M, Butterfield DA. Review: Alzheimer’s amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. J Struct Biol. 2000;130(2–3):184–208. ArticleCASPubMed Google Scholar
Butterfield DA. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review. Free Radic Res. 2002;36(12):1307–13. ArticleCASPubMed Google Scholar
Butterfield DA, Griffin S, Munch G, Pasinetti GM. Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer’s disease brain exists. J Alzheimers Dis. 2002;4(3):193–201. CASPubMed Google Scholar
Castellani R, Hirai K, Aliev G, Drew KL, Nunomura A, Takeda A, Cash AD, Obrenovich ME, Perry G, Smith MA. Role of mitochondrial dysfunction in Alzheimer’s disease. J Neurosci Res. 2002;70(3):357–60. ArticleCASPubMed Google Scholar
Spuch C, Ortolano S, Navarro C. New insights in the amyloid-Beta interaction with mitochondria. J Aging Res. 2012;2012:324968. ArticlePubMed CentralPubMed Google Scholar
Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003;161(1):41–54. ArticlePubMed CentralCASPubMed Google Scholar
Miranda S, Opazo C, Larrondo LF, Munoz FJ, Ruiz F, Leighton F, Inestrosa NC. The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer’s disease. Prog Neurobiol. 2000;62(6):633–48. ArticleCASPubMed Google Scholar
DiCiero Miranda M, de Bruin VM, Vale MR, Viana GS. Lipid peroxidation and nitrite plus nitrate levels in brain tissue from patients with Alzheimer’s disease. Gerontology. 2000;46(4):179–84. ArticleCASPubMed Google Scholar
Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, Bradshaw PC. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice. J Alzheimers Dis. 2010;20(Suppl 2):S535–50. PubMed Google Scholar
Lloret A, Fuchsberger T, Giraldo E, Vina J. Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer’s disease. Free Radic Biol Med. 2015;83:186–91. ArticleCASPubMed Google Scholar
Reddy PH. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer’s disease. J Neurochem. 2006;96(1):1–13. ArticleCASPubMed Google Scholar
Williams TI, Lynn BC, Markesbery WR, Lovell MA. Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer’s disease. Neurobiol Aging. 2006;27(8):1094–9. ArticleCASPubMed Google Scholar
Marmol F, Rodriguez CA, Sanchez J, Chamizo VD. Anti-oxidative effects produced by environmental enrichment in the hippocampus and cerebral cortex of male and female rats. Brain Res. 2015;10(1613):120–9. ArticleCAS Google Scholar
Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001;122(9):945–62. ArticleCASPubMed Google Scholar
Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer’s disease. J Neurochem. 2000;75(1):436–9. ArticleCASPubMed Google Scholar
Shringarpure R, Grune T, Davies KJ. Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells. Cell Mol Life Sci. 2001;58(10):1442–50. ArticleCASPubMed Google Scholar
Pratico D, Delanty N. Oxidative injury in diseases of the central nervous system: focus on Alzheimer’s disease. Am J Med. 2000;109(7):577–85. ArticleCASPubMed Google Scholar
Broe GA, Grayson DA, Creasey HM, Waite LM, Casey BJ, Bennett HP, Brooks WS, Halliday GM. Anti-inflammatory drugs protect against Alzheimer disease at low doses. Arch Neurol. 2000;57(11):1586–91. ArticleCASPubMed Google Scholar
Wu Q, Combs C, Cannady SB, Geldmacher DS, Herrup K. Beta-amyloid activated microglia induce cell cycling and cell death in cultured cortical neurons. Neurobiol Aging. 2000;21(6):797–806. ArticleCASPubMed Google Scholar
Benveniste EN, Nguyen VT, O’Keefe GM. Immunological aspects of microglia: relevance to Alzheimer’s disease. Neurochem Int. 2001;39(5–6):381–91. ArticleCASPubMed Google Scholar
Szczepanik AM, Funes S, Petko W, Ringheim GE. IL-4, IL-10 and IL-13 modulate A beta(1–42)-induced cytokine and chemokine production in primary murine microglia and a human monocyte cell line. J Neuroimmunol. 2001;113(1):49–62. ArticleCASPubMed Google Scholar
Akiyama H, Arai T, Kondo H, Tanno E, Haga C, Ikeda K. Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Dis Assoc Disord. 2000;14(Suppl 1):S47–53. ArticleCASPubMed Google Scholar
Raina AK, Zhu X, Rottkamp CA, Monteiro M, Takeda A, Smith MA. Cyclin’ toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J Neurosci Res. 2000;61(2):128–33. ArticleCASPubMed Google Scholar
Arendt T, Holzer M, Gartner U. Neuronal expression of cycline dependent kinase inhibitors of the INK4 family in Alzheimer’s disease. J Neural Transm. 1998;105(8–9):949–60. ArticleCASPubMed Google Scholar
Busser J, Geldmacher DS, Herrup K. Ectopic cell cycle proteins predict the sites of neuronal cell death in Alzheimer’s disease brain. J Neurosci. 1998;18(8):2801–7. CASPubMed Google Scholar
Giovanni A, Wirtz-Brugger F, Keramaris E, Slack R, Park DS. Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F × DP, B-amyloid-induced neuronal death. J Biol Chem. 1999;274(27):19011–6. ArticleCASPubMed Google Scholar
Yang Y, Geldmacher DS, Herrup K. DNA replication precedes neuronal cell death in Alzheimer’s disease. J Neurosci. 2001;21(8):2661–8. CASPubMed Google Scholar
Yang Y, Mufson EJ, Herrup K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci. 2003;23(7):2557–63. CASPubMed Google Scholar
Raina AK, Monteiro MJ, McShea A, Smith MA. The role of cell cycle-mediated events in Alzheimer’s disease. Int J Exp Pathol. 1999;80(2):71–6. ArticlePubMed CentralCASPubMed Google Scholar
Zhu X, Raina AK, Boux H, Simmons ZL, Takeda A, Smith MA. Activation of oncogenic pathways in degenerating neurons in Alzheimer disease. Int J Dev Neurosci. 2000;18(4–5):433–7. ArticleCASPubMed Google Scholar
Copani A, Condorelli F, Caruso A, Vancheri C, Sala A, Giuffrida Stella AM, Canonico PL, Nicoletti F, Sortino MA. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J. 1999;13(15):2225–34. CASPubMed Google Scholar
Copani A, Uberti D, Sortino MA, Bruno V, Nicoletti F, Memo M. Activation of cell-cycle-associated proteins in neuronal death: a mandatory or dispensable path? Trends Neurosci. 2001;24(1):25–31. ArticleCASPubMed Google Scholar
Majd S, Zarifkar A, Rastegar K, Takhshid MA. Different fibrillar Abeta 1-42 concentrations induce adult hippocampal neurons to reenter various phases of the cell cycle. Brain Res. 2008;1218:224–9. ArticleCASPubMed Google Scholar
Zhang M, Li J, Chakrabarty P, Bu B, Vincent I. Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice. Am J Pathol. 2004;165(3):843–53. ArticlePubMed CentralCASPubMed Google Scholar
Majd S, Chegini F, Chataway T, Zhou XF, Gai W. Reciprocal induction between alpha-synuclein and beta-amyloid in adult rat neurons. Neurotox Res. 2013;23(1):69–78. ArticlePubMed Google Scholar
Nagy Z. The last neuronal division: a unifying hypothesis for the pathogenesis of Alzheimer’s disease. J Cell Mol Med. 2005;9(3):531–41. ArticleCASPubMed Google Scholar
Tan CC, Yu JT, Tan MS, Jiang T, Zhu XC, Tan L. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiol Aging. 2014;35:941–57. ArticlePubMed Google Scholar
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839–40. ArticleCASPubMed Google Scholar
Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med. 2002;8(6):600–6. ArticleCASPubMed Google Scholar
Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol. 1996;55(3):259–72. ArticleCASPubMed Google Scholar
Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55(2):164–73. ArticleCASPubMed Google Scholar
George JM, Jin H, Woods WS, Clayton DF. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron. 1995;15(2):361–72. ArticleCASPubMed Google Scholar
Barbour R, Kling K, Anderson JP, Banducci K, Cole T, Diep L, Fox M, Goldstein JM, Soriano F, Seubert P, et al. Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis. 2008;5(2):55–9. ArticleCASPubMed Google Scholar
Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K. Demonstration of alpha-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol. 2002;176(1):98–104. ArticleCASPubMed Google Scholar
Recchia A, Debetto P, Negro A, Guidolin D, Skaper SD, Giusti P. Alpha-synuclein and Parkinson’s disease. FASEB J. 2004;18(6):617–26. ArticleCASPubMed Google Scholar
Perrin RJ, Woods WS, Clayton DF, George JM. Interaction of human alpha-Synuclein and Parkinson’s disease variants with phospholipids. Structural analysis using site-directed mutagenesis. J Biol Chem. 2000;275(44):34393–8. ArticleCASPubMed Google Scholar
Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, et al. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci. 2002;22(20):8797–807. CASPubMed Google Scholar
Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell. 2005;123(3):383–96. ArticleCASPubMed Google Scholar
Larsen KE, Schmitz Y, Troyer MD, Mosharov E, Dietrich P, Quazi AZ, Savalle M, Nemani V, Chaudhry FA, Edwards RH, et al. Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci. 2006;26(46):11915–22. ArticleCASPubMed Google Scholar
Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010;329(5999):1663–7. ArticlePubMed CentralCASPubMed Google Scholar
Alim MA, Hossain MS, Arima K, Takeda K, Izumiyama Y, Nakamura M, Kaji H, Shinoda T, Hisanaga S, Ueda K. Tubulin seeds alpha-synuclein fibril formation. J Biol Chem. 2002;277(3):2112–7. ArticleCASPubMed Google Scholar
Alim MA, Ma QL, Takeda K, Aizawa T, Matsubara M, Nakamura M, Asada A, Saito T, Kaji H, Yoshii M, et al. Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein. J Alzheimers Dis. 2004;6(4):435–42 (discussion 443–439). PubMed Google Scholar
Zhou RM, Huang YX, Li XL, Chen C, Shi Q, Wang GR, Tian C, Wang ZY, Jing YY, Gao C, et al. Molecular interaction of alpha-synuclein with tubulin influences on the polymerization of microtubule in vitro and structure of microtubule in cells. Mol Biol Rep. 2010;37(7):3183–92. ArticleCASPubMed Google Scholar
Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol. 2002;4(2):160–4. CASPubMed Google Scholar
Uversky VN. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation. J Neurochem. 2007;103(1):17–37. CASPubMed Google Scholar
Tenreiro S, Reimao-Pinto MM, Antas P, Rino J, Wawrzycka D, Macedo D, Rosado-Ramos R, Amen T, Waiss M, Magalhaes F, et al. Phosphorylation modulates clearance of alpha-synuclein inclusions in a yeast model of Parkinson’s disease. PLoS Genet. 2014;10:e1004302. ArticlePubMed CentralPubMedCAS Google Scholar
Mahul-Mellier AL, Fauvet B, Gysbers A, Dikiy I, Oueslati A, Georgeon S, Lamontanara AJ, Bisquertt A, Eliezer D, Masliah E, et al. c-Abl phosphorylates alpha-synuclein and regulates its degradation, implication for alpha-synuclein clearance and contribution to the pathogenesis of Parkinson’s Disease. Hum Mol Genet. 2014;23(11):2858–79. ArticlePubMed CentralCASPubMed Google Scholar
Tamo W, Imaizumi T, Tanji K, Yoshida H, Mori F, Yoshimoto M, Takahashi H, Fukuda I, Wakabayashi K, Satoh K. Expression of alpha-synuclein, the precursor of non-amyloid beta component of Alzheimer’s disease amyloid, in human cerebral blood vessels. Neurosci Lett. 2002;326(1):5–8. ArticleCASPubMed Google Scholar
Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ. Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One. 2008;3(4):e1867. ArticlePubMed CentralPubMedCAS Google Scholar
Paik SR, Shin HJ, Lee JH, Chang CS, Kim J. Copper(II)-induced self-oligomerization of alpha-synuclein. Biochem J. 1999;340(Pt 3):821–8. ArticlePubMed CentralCASPubMed Google Scholar
Hashimoto M, Hsu LJ, Xia Y, Takeda A, Sisk A, Sundsmo M, Masliah E. Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro. Neuroreport. 1999;10(4):717–21. ArticleCASPubMed Google Scholar
Murphy DD, Rueter SM, Trojanowski JQ, Lee VM. Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci. 2000;20(9):3214–20. CASPubMed Google Scholar
Zhu M, Li J, Fink AL. The association of alpha-synuclein with membranes affects bilayer structure, stability, and fibril formation. J Biol Chem. 2003;278(41):40186–97. ArticleCASPubMed Google Scholar
Jo E, Darabie AA, Han K, Tandon A, Fraser PE, McLaurin J. alpha-Synuclein-synaptosomal membrane interactions: implications for fibrillogenesis. Eur J Biochem. 2004;271(15):3180–9. ArticleCASPubMed Google Scholar
Scott D, Roy S. alpha-Synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis. J Neurosci. 2012;32(30):10129–35. ArticlePubMed CentralCASPubMed Google Scholar
Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT, McLean PJ, Unni VK. Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α- synuclein. J Neurosci. 2011;31:14508–20. ArticlePubMed CentralCASPubMed Google Scholar
Pan PY, Yue Z. Genetic causes of Parkinson’s disease and their links to autophagy regulation. Parkinsonism Relat Disord. 2014;20(Suppl 1):S154–7. ArticlePubMed Google Scholar
Iwata A, Miura S, Kanazawa I, Sawada M, Nukina N. alpha-Synuclein forms a complex with transcription factor Elk-1. J Neurochem. 2001;77(1):239–52. ArticleCASPubMed Google Scholar
Sidhu A, Wersinger C, Vernier P. Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse? FASEB J. 2004;18(6):637–47. ArticleCASPubMed Google Scholar
Iwata A, Maruyama M, Kanazawa I, Nukina N. alpha-Synuclein affects the MAPK pathway and accelerates cell death. J Biol Chem. 2001;276(48):45320–9. ArticleCASPubMed Google Scholar
Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, Tsuji S, Nukina N. Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum Mol Genet. 2003;12(20):2625–35. ArticleCASPubMed Google Scholar
Hunot S, Vila M, Teismann P, Davis RJ, Hirsch EC, Przedborski S, Rakic P, Flavell RA. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA. 2004;101(2):665–70. ArticlePubMed CentralCASPubMed Google Scholar
Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19(14):5782–91. CASPubMed Google Scholar
Levy OA, Malagelada C, Greene LA. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis. 2009;14(4):478–500. ArticlePubMed CentralPubMed Google Scholar
Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, Ravindranath V. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson’s disease: protection by alpha-lipoic acid. FASEB J. 2007;21(9):2226–36. ArticleCASPubMed Google Scholar
Klegeris A, Pelech S, Giasson BI, Maguire J, Zhang H, McGeer EG, McGeer PL. Alpha-synuclein activates stress signalling protein kinases in THP-1 cells and microglia. Neurobiol Aging. 2008;29(5):739–52. ArticleCASPubMed Google Scholar
Wilms H, Rosenstiel P, Romero-Ramos M, Arlt A, Schafer H, Seegert D, Kahle PJ, Odoy S, Claasen JH, Holzknecht C, et al. Suppression of MAP kinases inhibits microglial activation and attenuates neuronal cell death induced by alpha-synuclein protofibrils. Int J Immunopathol Pharmacol. 2009;22(4):897–909. CASPubMed Google Scholar
Camilleri A, Vassallo N. The centrality of mitochondria in the pathogenesis and treatment of Parkinson’s disease. CNS Neurosci Ther. 2014;20(7):591–602. ArticleCASPubMed Google Scholar
Eisbach SE, Outeiro TF. Alpha-synuclein and intracellular trafficking: impact on the spreading of Parkinson’s disease pathology. J Mol Med (Berl). 2013;91(6):693–703. ArticleCAS Google Scholar
Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD. Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol. 1994;36(3):348–55. ArticleCASPubMed Google Scholar
Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, Marsden CD. Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem. 1989;52(6):1830–6. ArticleCASPubMed Google Scholar
Spina MB, Cohen G. Dopamine turnover and glutathione oxidation: implications for Parkinson disease. Proc Natl Acad Sci USA. 1989;86(4):1398–400. ArticlePubMed CentralCASPubMed Google Scholar
Hsu LJ, Sagara Y, Arroyo A, Rockenstein E, Sisk A, Mallory M, Wong J, Takenouchi T, Hashimoto M, Masliah E. alpha-Synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol. 2000;157(2):401–10. ArticlePubMed CentralCASPubMed Google Scholar
Li WW, Yang R, Guo JC, Ren HM, Zha XL, Cheng JS, Cai DF. Localization of alpha-synuclein to mitochondria within midbrain of mice. Neuroreport. 2007;18(15):1543–6. ArticleCASPubMed Google Scholar
Parihar MS, Parihar A, Fujita M, Hashimoto M, Ghafourifar P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci. 2008;65(7–8):1272–84. ArticleCASPubMed Google Scholar
Dryanovski D, Guzman J, Xie Z, Galteri D, Volpicelli-Daley L, Lee V, Miller R, Schumacker P, Surmeier D. Calcium entry and α-synuclein inclusions elevate dendritic mitochondrial oxidant stress in dopaminergic neurons. J Neurosci. 2013;33(24):10154–64. ArticlePubMed CentralCASPubMed Google Scholar
Zaltieri M, Longhena F, Pizzi M, Missale C, Spano P, Bellucci A. Mitochondrial Dysfunction and α-synuclein Synaptic Pathology in Parkinson’s Disease: Who’s on First. Parkinsons Dis. 2015;108029:1–10. Article Google Scholar
Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996;86(1):147–57. ArticleCASPubMed Google Scholar
Thayanidhi N, Helm JR, Nycz DC, Bentley M, Liang Y, Hay JC. Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell. 2010;21(11):1850–63. ArticlePubMed CentralCASPubMed Google Scholar
Colla E, Jensen PH, Pletnikova O, Troncoso JC, Glabe C, Lee MK. Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum occurs in alpha-synucleinopathy in vivo. J Neurosci. 2012;32(10):3301–5. ArticlePubMed CentralCASPubMed Google Scholar
Foran PG, Mohammed N, Lisk GO, Nagwaney S, Lawrence GW, Johnson E, Smith L, Aoki KR, Dolly JO. Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem. 2003;278(2):1363–71. ArticleCASPubMed Google Scholar
Chen L, Jin J, Davis J, Zhou Y, Wang Y, Liu J, Lockhart PJ, Zhang J. Oligomeric alpha-synuclein inhibits tubulin polymerization. Biochem Biophys Res Commun. 2007;356(3):548–53. ArticleCASPubMed Google Scholar
Soper JH, Roy S, Stieber A, Lee E, Wilson RB, Trojanowski JQ, Burd CG, Lee VM. Alpha-synuclein-induced aggregation of cytoplasmic vesicles in Saccharomyces cerevisiae. Mol Biol Cell. 2008;19(3):1093–103. ArticlePubMed CentralCASPubMed Google Scholar
Gosavi N, Lee HJ, Lee JS, Patel S, Lee SJ. Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion. J Biol Chem. 2002;277(50):48984–92. ArticleCASPubMed Google Scholar
Lee HJ, Khoshaghideh F, Lee S, Lee SJ. Impairment of microtubule-dependent trafficking by overexpression of alpha-synuclein. Eur J Neurosci. 2006;24(11):3153–62. ArticlePubMed Google Scholar
Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron. 2010;65(1):66–79. ArticlePubMed CentralCASPubMed Google Scholar
Saha AR, Hill J, Utton MA, Asuni AA, Ackerley S, Grierson AJ, Miller CC, Davies AM, Buchman VL, Anderton BH, et al. Parkinson’s disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci. 2004;117(Pt 7):1017–24. ArticleCASPubMed Google Scholar
Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, Kondo J, Ihara Y, Saitoh T. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci USA. 1993;90(23):11282–6. ArticlePubMed CentralCASPubMed Google Scholar
Yu S, Li X, Liu G, Han J, Zhang C, Li Y, Xu S, Liu C, Gao Y, Yang H, et al. Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience. 2007;145(2):539–55. ArticleCASPubMed Google Scholar
Paleologou KE, Kragh CL, Mann DM, Salem SA, Al-Shami R, Allsop D, Hassan AH, Jensen PH, El-Agnaf OM. Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. Brain. 2009;132(Pt 4):1093–101. PubMed Google Scholar
Yang Y, Varvel NH, Lamb BT, Herrup K. Ectopic cell cycle events link human Alzheimer’s disease and amyloid precursor protein transgenic mouse models. J Neurosci. 2006;26(3):775–84. ArticleCASPubMed Google Scholar
Gallardo G, Schluter OM, Sudhof TC. A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides. Nat Neurosci. 2008;11(3):301–8. ArticleCASPubMed Google Scholar