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Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein
Abstract
Alpha-synuclein (alpha-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that alpha-syn induces fibrillization of tau and that coincubation of tau and alpha-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of alpha-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human alpha-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human alpha-syn plus P301L mutant tau. This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.
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“Evidence suggests that Aβ can directly affect α-synuclein toxicity, and it is also known that tau protein and α-synuclein can directly interact promoting their co-assembly [124–126].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [125]
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Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
Self-citationMcKeith, I. G., Galasko, D., Kosaka, K., Perry, E. K., Dickson, D. W., Hansen, L. A., Salmon, D. P., Lowe, J., Mirra, S. S., Byrne, E. J., et al. (1996) · Neurology · doi:10.1212/wnl.47.5.1113 · Cited by 3,960
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Self-citationGoedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., & Crowther, R. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90210-9 · Cited by 2,492
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480
Self-citationBuée, L., Bussière, T., Buée‐Scherrer, V., Delacourte, A., & Hof, P. R. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00019-9 · Cited by 2,142
NACP, A Protein Implicated in Alzheimer's Disease and Learning, Is Natively Unfolded
Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., & Lansbury, P. T. (1996) · Biochemistry · doi:10.1021/bi961799n · Cited by 1,524
Conway, K. A., Harper, J. D., & Lansbury, P. T. (1998) · Nature Medicine · doi:10.1038/3311 · Cited by 1,520
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371
Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein
Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00682-7 · Cited by 1,266
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Flagged first, then by citations
Research works printed but not linked: 2
- L. Hansen et al., Neurology40, 1 (1990).
- C. Richter-Landsberg, M. Gorath, J. Q. Trojanowski, V.M.-Y. Lee, J. Neurosci. Res.62, 914 (2000).
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Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,497
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329
Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Zimprich, A. A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M. J., Lincoln, S., Kachergus, J. M., Hulihan, M., Uitti, R. J., Calne, D. B., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.005 · Cited by 3,087
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563
Self-citationThe Amyloid State of Proteins in Human Diseases
Eisenberg, D. S., & Jucker, M. (2012) · Cell · doi:10.1016/j.cell.2012.02.022 · Cited by 1,769
Molecular Pathways of Neurodegeneration in Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2003) · Science · doi:10.1126/science.1087753 · Cited by 1,674
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
“In fact, each one of these two proteins has the tendency to seed the aggregation of the other (Giasson et al. 2003). a-Synuclein appears to enhance tau phosphorylation, and this may lead to secondary effects on the microtubular network (Jensen et al. 1999; Haggerty et al. 2011; Qureshi and Paudel…”
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Moore, D. J., West, A. B., Dawson, V. L., & Dawson, T. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135718 · Cited by 1,304
“…suggests that interactions between α-synuclein and tau synergistically promote the fibrillization of both proteins in vitro and in animal models (Giasson et al. 2003), which is supported by the co-occurrence of α-synuclein and tau pathology in some monogenic forms of PD, in other…”
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Maji, S. K., Perrin, M. H., Sawaya, M. R., Jessberger, S., Vadodaria, K. C., Rissman, R. A., Singru, P. S., Nilsson, K. P. R., Simon, R. A., Schubert, D. A., et al. (2009) · Science · doi:10.1126/science.1173155 · Cited by 1,074
Distinct Tau Prion Strains Propagate in Cells and Mice and Define Different Tauopathies
Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., Barker, S. J., Foley, A. C., Thorpe, J. R., Serpell, L. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.047 · Cited by 986
“Prior reports have indicated that in certain cases, a-synuclein aggregates can cross-seed FL tau (Giasson et al., 2003; Guo et al., 2013;Waxman and Giasson, 2011).”
BackgroundRoles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Role of tau protein in both physiological and pathological conditions
AVILA, J., LUCAS, J. J., PÉREZ, M., & HERNÁNDEZ, F. (2004) · Physiological Reviews · doi:10.1152/physrev.00024.2003 · Cited by 1,005
“Avila, unpublished data), and -synuclein has also been seen to facilitate tau assembly (79).”
BackgroundNeuropathological assessment of Parkinson’s disease: refining the diagnostic criteria
Dickson, D. W., Braak, H., Duda, J. E., Duyckaerts, C., Gasser, T., Halliday, G. M., Hardy, J., Leverenz, J. B., Del Tredici, K., Wszolek, Z. K., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70238-8 · Cited by 972
The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort
Williams‐Gray, C. H., Evans, J., Goris, A., Foltynie, T., Ban, M., Robbins, T. W., Brayne, C., Kolachana, B. S., Weinberger, D. R., Sawcer, S. J., et al. (2009) · Brain · doi:10.1093/brain/awp245 · Cited by 1,017
“Third, tau and alpha-synuclein have been shown to interact and fibrillize synergistically in vitro (Giasson et al., 2003).”
BackgroundTDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador‐Ortiz, C., Lin, W., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff‐Radford, N. R., Hutton, M. L., & Dickson, D. W. (2007) · Annals of Neurology · doi:10.1002/ana.21154 · Cited by 916
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897
Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies
Irwin, D. J., Lee, V. M. ‐., & Trojanowski, J. Q. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3549 · Cited by 914
Self-citationOxidative Stress and Neurotoxicity
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Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696
Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Forman, M. S., Trojanowski, J. Q., & Lee, V. M.-Y. (2004) · Nature Medicine · doi:10.1038/nm1113 · Cited by 715
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Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?
Compta, Y., Parkkinen, L., O’Sullivan, S. S., Vandrovcová, J., Holton, J. L., Collins, C., Lashley, T., Kallis, C., Williams, D. R., de Silva, R., et al. (2011) · Brain · doi:10.1093/brain/awr031 · Cited by 607
“…inclusions (perikaryal Lewy bodies and Lewy neurites) has also been proposed as a critical determinant (Masliah et al., 2001; Apaydin et al., 2002; Giasson et al., 2003; Pletnikova et al., 2005; Lashley et al., 2008, Clinton et al., 2010), and a link between concomitant Alzheimer’s disease…”
Cell Biology and Pathophysiology of α-SynucleinPreprint
Burré, J., Sharma, M., & Südhof, T. C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024091 · Cited by 626
Clinton, L. K., Blurton-Jones, M., Myczek, K., Trojanowski, J. Q., & LaFerla, F. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0490-10.2010 · Cited by 576
“Importantly, plaques, tangles, and LBs do not develop in high enough individual frequency to explain their co-occurrence simply by statistical overlap; thus, it has been hypothesized that A , tau, and -syn promote the accumulation of one another (Giasson et al., 2003; Lee et al., 2004).”
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Self-citationNeuropathologic substrates of Parkinson disease dementia
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Self-citationWakabayashi, K., Tanji, K., Mori, F., & Takahashi, H. (2007) · Neuropathology · doi:10.1111/j.1440-1789.2007.00803.x · Cited by 544
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BackgroundAlzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502
Shults, C. W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509567103 · Cited by 495
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Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0261-2 · Cited by 468
Self-citationEdwards, T. L., Scott, W. K., Almonte, C., Burt, A., Powell, E. H., Beecham, G. W., Wang, L., Zuchner, S. L., Konidari, I., Wang, G., et al. (2010) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2009.00560.x · Cited by 471
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“which might synergistically promote their mutual aggregation and vice versa.(34,124,162) In vivo interactions between aSyn and tau are supported by genetic studies,(57,163) and in familial PD, fibrillation of aSyn and tau is caused by the A53T aSyn mutation.”
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BackgroundZou, W., Pu, T., Feng, W., Lu, M., Zheng, Y., Du, R., Xiao, M., & Hu, G. (2019) · Translational Neurodegeneration · doi:10.1186/s40035-019-0147-y · Cited by 396
Rey, N. L., Steiner, J. A., Maroof, N., Luk, K. C., Madaj, Z., Trojanowski, J. Q., Lee, V. M. ‐., & Brundin, P. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160368 · Cited by 400
Self-citationDementia with Lewy bodies: an update and outlook
Outeiro, T. F., Koss, D. J., Erskine, D., Walker, L., Kurzawa-Akanbi, M., Burn, D., Donaghy, P., Morris, C., Taylor, J.-P., Thomas, A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0306-8 · Cited by 381
Oueslati, A. (2016) · Journal of Parkinson s Disease · doi:10.3233/jpd-160779 · Cited by 385
Kang, J. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.3861 · Cited by 366
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BackgroundKovács, G. G., Milenković, I., Wöehrer, A., Höftberger, R., Gelpí, E., Haberler, C., Hönigschnabl, S., Reiner‐Concin, A., Heinzl, H., Jungwirth, S., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1157-y · Cited by 380
“1 3 It has been hypothesised that Aβ, tau, and α-synuclein mutually promote their accumulation [17, 33].”
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Zhou, W., Zhu, M., Wilson, M. A., Petsko, G. A., & Fink, A. L. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.12.030 · Cited by 361
Oueslati, A., Fournier, M., & Lashuel, H. A. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)83007-9 · Cited by 354
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Tracy, T. E., Madero‐Pérez, J., Swaney, D. L., Chang, T. S., Moritz, M., Konràd, C., Ward, M. E., Stevenson, E. J., Hüttenhain, R., Kauwe, G., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.041 · Cited by 355
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Self-citationThe Epidemiology of Dementia Associated with Parkinson's Disease
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“Interestingly, a gene–gene interaction between MAPT and SNCA (31), co-localization of alpha-synuclein and tau protein within the Lewy bodies in PD (43) and synergistic fibrillization observed in vitro (30) were also reported.”
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“Specific coaggregation of some hormones might be possible (Maji et al. 2009b) because amyloid peptides are able to cross-seed (Han et al. 1995; Giasson et al. 2003), which would also eventually result in a defined hormone release ratio.”
BackgroundAlzheimer Disease With Amygdala Lewy Bodies: A Distinct Form of α-Synucleinopathy
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“Giasson et al pointed out that tau and >-synuclein may reciprocally promote aggregation in vitro (42).”
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BackgroundPaleologou, K. E., Oueslati, A., Shakked, G., Rospigliosi, C. C., Kim, H., Lamberto, G. R., Fernández, C. O., Schmid, A. W., Chegini, F., Gai, W., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5922-09.2010 · Cited by 339
“The C-terminal region of -syn has been implicated in the majority of -syn interactions with proteins (Jensen et al., 1999; Giasson et al., 2003; Fernández et al., 2004) and metal ions (Paik et al.”
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Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Jackson, G. R., & Kayed, R. (2010) · Biochemistry · doi:10.1021/bi1016233 · Cited by 359
Mechanisms of secretion and spreading of pathological tau protein
Brunello, C. A., Merezhko, M., Uronen, R.-L., & Huttunen, H. J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03349-1 · Cited by 304
Yazawa, I., Giasson, B. I., Sasaki, R., Zhang, B., Joyce, S., Uryu, K., Trojanowski, J. Q., & Lee, V. M.-Y. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.032 · Cited by 301
Self-citationSengupta, U., & Kayed, R. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102270 · Cited by 318
“Several groups including ours demonstrated α-Syn/tau direct interaction forming aggregates reflecting cross-seeding mechanism in vitro (Gerson et al., 2018; Giasson et al., 2003; Hojjatian et al., 2021; Lasagna-Reeves et al., 2010; Sengupta et al., 2020).”
BackgroundOxidative Stress in Neurodegeneration
Shukla, V., Mishra, S. K., & Pant, H. C. (2011) · Advances in Pharmacological Sciences · doi:10.1155/2011/572634 · Cited by 303
Alpha-synuclein and tau: teammates in neurodegeneration?
Moussaud, S., Jones, D. R., Moussaud-Lamodière, E. L., Delenclos, M., Ross, O. A., & McLean, P. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-43 · Cited by 301
“Likewise, cognitive deficits and tauopathy have been observed in αsyn-overexpressing PD models [100-103].”
BackgroundInfluentialPrion-like disorders: blurring the divide between transmissibility and infectivity
Cushman-Nick, M., Johnson, B. S., King, O. D., Gitler, A. D., & Shorter, J. (2010) · Journal of Cell Science · doi:10.1242/jcs.051672 · Cited by 301
“composed singly of tau or -synuclein, except for a few instances in which spatially segregated portions of a fiber were labeled positive for either tau or -synuclein (Giasson et al., 2003a).”
BackgroundInfluentialHead injury and Parkinson's disease risk in twins
Goldman, S. M., Tanner, C. M., Oakes, D., Bhudhikanok, G. S., Gupta, A., & Langston, J. W. (2006) · Annals of Neurology · doi:10.1002/ana.20882 · Cited by 297
Wacker, J. L., Zareie, M. H., Fong, H. K., Sarıkaya, M., & Muchowski, P. J. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb860 · Cited by 286
Tsigelny, I. F., Crews, L., Desplats, P., Shaked, G. M., Sharikov, Y., Mizuno, H., Spencer, B., Rockenstein, E., Trejo, M., Platoshyn, O., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003135 · Cited by 281
“abnormal conditions [91].”
RetractedRecent advances in our understanding of neurodegeneration
Jellinger, K. A. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0240-y · Cited by 274
“The mechanism by which aSyn, tau, and Ab protein make fibrils is an example of conformational plasticity, because these polypeptides can visit a coil or helical structure, but otherwise they convert into a pathogenic b-sheet structure highly suitable for polymerization and fiber formation (Cairns et al. 2004; Cookson…”
BackgroundIntegrating Pathways of Parkinson's Disease in a Molecular Interaction Map
Fujita, K., Ostaszewski, M., Matsuoka, Y., Ghosh, S., Glaab, E., Trefois, C., Crespo, I., Perumal, T. M., Jurkowski, W., Antony, P. M. A., et al. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8489-4 · Cited by 276
“Axonal transport might be impaired by misfolded α-syn through perturbation of microtubule assembly [135–137], especially together with MAPT protein [138–143].”
BackgroundTemplate-assisted filament growth by parallel stacking of tau
Margittai, M., & Langen, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401911101 · Cited by 276
The neuropathology, pathophysiology and genetics of multiple system atrophy
Ahmed, Z., Asi, Y. T., Sailer, A., Lees, A. J., Houlden, H., Révész, T., & Holton, J. L. (2011) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2011.01234.x · Cited by 275
Tau and α‐synuclein in susceptibility to, and dementia in, Parkinson's disease
Goris, A., Williams‐Gray, C. H., Clark, G. R., Foltynie, T., Lewis, S. J. G., Brown, J., Ban, M., Spillantini, M. G., Compston, A., Burn, D. J., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21192 · Cited by 273
“In vitro experiments have demonstrated that -synuclein is able to initiate tau fibrillization, after which -synuclein and tau synergistically promote fibrillization.(43) Our findings of an interaction between SNCA and MAPT increasing risk for idiopathic PD lend further support to the intersection of the tau and -synuc…”
BackgroundPrevalence and impact of vascular and Alzheimer pathologies in Lewy body disease
Jellinger, K. A., & Attems, J. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0347-5 · Cited by 267
“... disorders [57, 78], and the association between dopaminergic neuronal degeneration, accumulation of Syn and tau or both proteins in LRRK2 mutations [1, 29, 102], induction of hyperphosphorylation of tau by Syn in the MPTP model of parkinsonism [23], and the association of atypical protein kinase C (aPKC) and phosp…”
BackgroundInterface between tauopathies and synucleinopathies: A tale of two proteins
Galpern, W. R., & Lang, A. E. (2006) · Annals of Neurology · doi:10.1002/ana.20819 · Cited by 267
“Mice overexpressing human A53T SNCA not only demonstrate inclusions that stain for AS, but also have inclusions that stain for tau, and indeed some of the inclusions stain for both proteins.(120) Transgenic mice expressing both wild-type human SNCA and P301L mutant tau also demonstrate intracellular inclusions compose…”
BackgroundInfluentialGuo, J., Arai, T., Miklossy, J., & McGeer, P. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509386103 · Cited by 260
Lewy body-related ?-synucleinopathy in the aged human brain
Jellinger, K. A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0138-7 · Cited by 253
Sardi, S. P., Clarke, J. L., Viel, C., Chan, M., Tamsett, T. J., Treleaven, C. M., Bu, J., Sweet, L., Passini, M. A., Dodge, J. C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220464110 · Cited by 252
“However, the disease mechanisms need further clarification, because α-synuclein fibrils may be able to promote the polymerization of tau (24, 38), so the observed tau aggregation in the CNS of Gba1 mice may be occurring secondary to α-synuclein fibrillation.”
BackgroundBassil, F., Brown, H. J., Pattabhiraman, S., Iwasyk, J. E., Maghames, C. M., Meymand, E. S., Cox, T. O., Riddle, D. M., Zhang, B., Trojanowski, J. Q., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.10.010 · Cited by 246
“First, Aβ plaques induce pooling of α-syn within the synaptic terminals which is “primed” to cross-seed other aggregation prone proteins like tau (Giasson et al., 2003; Guo et al., 2013).”
InfluentialSelf-citationHeat Shock Prevents Alpha-synuclein-induced Apoptosis in a Yeast Model of Parkinson's Disease
Flower, T. R., Chesnokova, L. S., Froelich, C. A., Dixon, C., & Witt, S. N. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.06.060 · Cited by 239
The natural history of treated Parkinson's disease in an incident, community based cohort
Evans, J., Mason, S., Williams‐Gray, C. H., Foltynie, T., Brayne, C., Robbins, T. W., & Barker, R. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2011.240366 · Cited by 235
Protein phosphorylation in neurodegeneration: friend or foe?
Tenreiro, S., Eckermann, K., & Outeiro, T. F. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00042 · Cited by 252
“Glycogen synthase kinase-3β (GSK-3β) activation was proposed as mediator of Aβ42 oligomer-induced effects on tau phosphorylation in P301L mice (Selenica et al., 2013).”
BackgroundInfluentialA critical evaluation of current staging of α-synuclein pathology in Lewy body disorders
Jellinger, K. A. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.07.006 · Cited by 247
“, in LRRK2 mutations [144] and in animal models of PD [145], with association of phospo-tau and αSyn in both NFTs and LBs [146] and in vitro promotion of tau aggregation by αSyn and vice versa [147].”
BackgroundA critical reappraisal of current staging of Lewy-related pathology in human brain
Jellinger, K. A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0406-y · Cited by 240
The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson's Disease Dementia
Yang, L., Wang, H., Liu, L., & Xie, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00073 · Cited by 236
“On one hand, low concentrations of α-synuclein do not fibrillate until tau is present (Giasson et al., 2003).”
BackgroundCholesterol homeostasis in neurons and glial cells
Vance, J. E., Hayashi, H., & Karten, B. (2005) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2005.01.005 · Cited by 225
Initiative, T. P. P. M., Kang, J., Mollenhauer, B., Coffey, C. S., Toledo, J. B., Weintraub, D. A., Galasko, D. R., Irwin, D. J., Deerlin, V. M. V., Chen‐Plotkin, A. S., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1552-2 · Cited by 225
“Basic research and neuropathology studies have suggested interaction between α-syn and tau in the brain [7, 8, 10, 43], which are further supported by our findings of a significant correlation between CSF α-syn and tau.”
Self-citationNeurogenesis in aging and age-related neurodegenerative diseases
Čulig, L., Chu, X., & Bohr, V. A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101636 · Cited by 235
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220
“The tau subsequently aggregates which could promote the pathological pathway in synergy [542,543].”
BackgroundCerebrospinal fluid biomarkers in Parkinson disease
Parnetti, L., Castrioto, A., Chiasserini, D., Persichetti, E., Tambasco, N., El-Agnaf, O., & Calabresi, P. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.10 · Cited by 209
Aβ deposition is associated with enhanced cortical α-synuclein lesions in Lewy body diseases
Pletniková, O., West, N. C., Lee, M. K., Rudow, G. L., Skolasky, R. L., Dawson, T. M., Marsh, L., & Troncoso, J. C. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.10.006 · Cited by 210
α-Synuclein: Normal Function and Role in Neurodegenerative Diseases
Norris, E. H., Giasson, B. I., & Lee, V. M. ‐. (2004) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)60002-0 · Cited by 208
Self-citationGlucosylceramide synthase inhibition alleviates aberrations in synucleinopathy models
Sardi, S. P., Viel, C., Clarke, J., Treleaven, C. M., Richards, A. M., Park, H., Olszewski, M. A., Dodge, J. C., Marshall, J., Makino, E., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616152114 · Cited by 203
Metadata
- Authors
- Giasson, B. I., Forman, M. S., Higuchi, M., Golbe, L. I., Graves, C. L., Kotzbauer, P. T., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Lee, Virginia M.-Y.
- ORCID
- Venue
- Science
- Published
- 2003-04-25
- Volume
- 300
- Issue
- 5619
- Pages
- 636-640
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2073893553
- Cited by
- 879
- References
- 27
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 37 · 2023: 35 · 2022: 58 · 2021: 32 · 2020: 50 · 2019: 52 · 2018: 49 · 2017: 42 · 2016: 35 · 2015: 31 · 2014: 39 · 2013: 42 · 2012: 33
- FWCI
- 26.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- alpha-synuclein, tau protein, amyloid fibril formation, protein aggregation, neurodegenerative diseases, synucleinopathies, tauopathy, oligodendrocytes, P301L tau, A53T alpha-synuclein, transgenic mouse model, intraneuronal inclusions
- MeSH terms
- Amyloid, Animals, Biopolymers, Brain Chemistry, Humans, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Oligodendroglia, Protein Conformation, Microscopy, Immunoelectron, tau Proteins, Neurodegenerative Diseases, Protein Isoforms, Tauopathies, Mice, Synucleins, alpha-Synuclein
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