The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
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
Self-citation
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).
Cited by
Sorted by citations
Items 401–500 of 879
Prion Strain Interactions Are Highly Selective
Nilsson, K. P. R., Joshi-Barr, S., Winson, O., & Sigurdson, C. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2417-10.2010 · Cited by 41
“Similar to our finding of both independent and hybrid mNS and mCWD plaques, -synuclein and tau can also develop independently or together in patients and in transgenic mice with -synuclein mutations, and can promote the fibrillization of each other in vitro (Giasson et al., 2003).”
BackgroundResultInfluentialXin, W., Emadi, S., Williams, S. M., Liu, Q., Schulz, P., He, P., Alam, N. B., Wu, J., & Sierks, M. R. (2015) · Biomolecules · doi:10.3390/biom5031634 · Cited by 40
“The -synuclein protein occurs in vivo in various forms and morphologies [8,38,39], and can interact with membranes [40–42], other proteins such as tau, p25alpha, tubulin, and transcription factor ELK-1 [43–45], metal ions including aluminum, copper, calcium, and iron [19], and catecholamines such as dopamine [15,46].”
BackgroundTau and α-Synuclein Inclusions in a Case of Familial Frontotemporal Dementia and Progressive Aphasia
Yancopoulou, D., Xuereb, J. H., Crowther, R. A., Hodges, J. R., & Spillantini, M. G. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.3.245 · Cited by 40
“As the coexistence of tau and a-synuclein inclusions has been recently described in several cases of neurodegenerative diseases, some studies have investigated the existence of a synergistic effect in the abnormal aggregation of the two proteins (42).”
BackgroundHuang, X., Wen, M., Ng, S. Y., Hartono, S., Chia, N. S. Y., Choi, X., Tay, K. Y., Au, W., Chan, L. L., Tan, E., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14192 · Cited by 40
Heterotypic Amyloid β interactions facilitate amyloid assembly and modify amyloid structure
Konstantoulea, K., Guerreiro, P. S., Ramakers, M., Louros, N. N., Aubrey, L. D., Houben, B., Michiels, E., Vleeschouwer, M. D., Lampi, Y., Ribeiro, L. F., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108591 · Cited by 39
“…self-specificity is not absolute and that disease amyloids can engage heterotypic interactions resulting in cross-seeding and co-aggregation (Giasson et al , 2003; Oskarsson et al , 2015; Lutter et al , 2019; Konstantoulea et al , 2021; Ly et al , 2021) that are relevant to the…”
Lorenzo, D. D. (2024) · ChemMedChem · doi:10.1002/cmdc.202400180 · Cited by 46
Ciaccioli, G., Martins, A., Rodrigues, C., Vieira, H., & Calado, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055848 · Cited by 40
“In fact, in a double transgenic mice expressing human ASYN WT in combination with human P301L mutant tau, these two proteins have been shown to co-localize in the same intracellular inclusions [27].”
BackgroundBerlyand, Y., Weintraub, D. A., Xie, S. X., Mellis, I. A., Doshi, J. J., Rick, J. H., McBride, J. D., Davatzikos, C. A., Shaw, L. M. J., Hurtig, H. I., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147319 · Cited by 39
Self-citationProtein Partners of α‐Synuclein in Health and Disease
Lassen, L. B., Reimer, L., Ferreira, N., Betzer, C., & Jensen, P. H. (2016) · Brain Pathology · doi:10.1111/bpa.12374 · Cited by 39
“Tau inclusions are found in some Parkinson patients (26), and the binding between Tau and AS increases the aggregation propensity of both proteins (38).”
BackgroundCSF biomarkers in neurodegenerative and vascular dementias
Llorens, F., Schmitz, M., Ferrer, I., & Zerr, I. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.03.003 · Cited by 44
“It is worth noting that a-synuclein is able to bind tau, thus stimulating its phosphorylation (Jensen et al., 1999) and fibrillation (Giasson et al., 2003).”
BackgroundDaniele, S., Pietrobono, D., Fusi, J., Iofrida, C., Chico, L., Petrozzi, L., Gerfo, A. L., Baldacci, F., Galetta, F., Siciliano, G., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0523-5 · Cited by 41
Sengupta, U., Puangmalai, N., Bhatt, N. N., García, S., Zhao, Y., & Kayed, R. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01913-6 · Cited by 38
Werner, T., Horváth, I., & Wittung-Stafshede, P. E. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-202085 · Cited by 40
Selectivity of Lewy body protein interactions along the aggregation pathway of α-synuclein
Leitao, A. D. G., Rudolffi-Soto, P., Chappard, A., Bhumkar, A., Lau, D., Hunter, D. J. B., Gambin, Y., & Sierecki, E. (2021) · Communications Biology · doi:10.1038/s42003-021-02624-x · Cited by 41
Lewis, K. A., Su, Y., Jou, O., Ritchie, C. M., Foong, C., Hynan, L. S., White, C. L., Thomas, P., & Hatanpaa, K. J. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100552 · Cited by 41
α-synuclein interacts with SOD1 and promotes its oligomerization
Helferich, A. M., Ruf, W. P., Grozdanov, V., Freischmidt, A., Feiler, M. S., Zondler, L., Ludolph, A. C., McLean, P. J., Weishaupt, J. H., & Danzer, K. M. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0062-3 · Cited by 37
“Cross-seeding effects of α-synuclein with other relevant neurodegenerative disease proteins like tau and amyloid-β have already been described [45, 46].”
BackgroundYue, Y., Zhang, X., Lv, W., Lai, H., & Shen, T. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.390970 · Cited by 38
“Furthermore, in vitro experiments have shown that tau and α-synuclein can promote the polymerization and fibril formation of the other (Giasson et al., 2003).”
BackgroundRole for the microtubule-associated protein tau variant p.A152T in risk of α-synucleinopathies
Labbé, C., Ogaki, K., Lorenzo‐Betancor, O., Soto‐Ortolaza, A. I., Walton, R. L., Rayaprolu, S., Fujioka, S., Murray, M. E., Heckman, M. G., Puschmann, A., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001946 · Cited by 38
“Furthermore, it has been shown that tau and a-synuclein synergistically promote the polymerization of each other in vitro.(24) The overlapping pathologies could be interpreted as an indication that some molecular pathways involved in these disease pathogeneses are the same and that MAPT p.”
BackgroundInteractions Between α-Synuclein and Tau Protein: Implications to Neurodegenerative Disorders
Li, X., James, S., & Lei, P. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0829-1 · Cited by 39
Recent Insights on Alzheimer’s Disease Originating from Yeast Models
Seynnaeve, D., Vecchio, M. D., Fruhmann, G., Verelst, J., Cools, M., Beckers, J., Mulvihill, D. P., Winderickx, J., & Franssens, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19071947 · Cited by 39
Padilla-Godínez, F. J., Vázquez-García, E. R., Trujillo-Villagrán, M. I., Soto-Rojas, L. O., Palomero‐Rivero, M., Hernández-González, O., Pérez-Eugenio, F., Collazo-Navarrete, O., Arias-Carrión, Ó., & Guerra‐Crespo, M. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1570553 · Cited by 42
“The negatively charged C-terminus of α -syn interacts with tau’s microtubule-binding domain, enhancing each other’s aggregation potential by destabilizing proteostasis (Jensen et al., 1999; Giasson et al., 2003; Nonaka et al., 2010; Lu et al., 2020; Yan et al., 2020).”
SNCA,MAPT, andGSK3Bin Parkinson disease: a gene-gene interaction study
Wider, C. W., Vilariño‐Güell, C., Heckman, M. G., Jasinska-Myga, B., Ortolaza-Soto, A. I., Diehl, N. N., Crook, J. E., Cobb, S. A., Bacon, J. A., Aasly, J. O., et al. (2010) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.03297.x · Cited by 37
“One study found that a-synuclein induces fibrillization of tau and that co-incubation of a-synuclein and tau synergistically promotes fibrillization of both proteins [10].”
BackgroundHippocampal Sclerosis of Aging Can Be Segmental
Ighodaro, E. T., Jicha, G. A., Schmitt, F. A., Neltner, J. H., Abner, E. L., Kryscio, R. J., Smith, C. D., Duplessis, T., Anderson, S., Patel, E., et al. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000204 · Cited by 37
Zhang, M., Hu, R., Liang, G., Chang, Y., Sun, Y. P., Peng, Z., & Zheng, J. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp5022246 · Cited by 39
Nie, S., Ma, K., Sun, M., Lee, M., Yang, T., Chen, G., Zhang, Z., Zhang, Z., & Cao, X. (2019) · Parkinson s Disease · doi:10.1155/2019/9193534 · Cited by 37
“α-synuclein is a necessary condition for provoking phosphorylation and aggregation of tau protein in vitro, showing that α-synuclein may trigger the initiation of tauopathy [42].”
BackgroundLaferrière, F., Claverol, S., Bézard, E., Giorgi, F. D., & Ichas, F. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-021-00264-w · Cited by 36
Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors
Sarell, C. J., Woods, L. A., Su, Y., Debelouchina, G. T., Ashcroft, A. E., Griffin, R. G., Stockley, P. G., & Radford, S. E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.447524 · Cited by 37
Role of gamma-synuclein in microtubule regulation
Zhang, H., Kouadio, A., Cartledge, D. M., & Godwin, A. K. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.10.013 · Cited by 37
“Alpha-synuclein seeds the fibrillization of tau in vitro and coincubation of alpha-synuclein and tau promoted the fibrillization of both proteins [24].”
BackgroundFujishiro, H., Imamura, A., Lin, W.-L., Uchikado, H., Mark, M. H., Golbe, L. I., Markopoulou, K., Wszołek, Z. K., & Dickson, D. W. (2013) · Europe PMC (PubMed Central) · Cited by 37
Self-citationKuang, Y., Mao, H., Huang, X., Chen, M., Dai, W. H., Gan, T., Wang, J., Sun, H., Lin, H., Liu, Q., et al. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00449-2 · Cited by 37
“Research has demonstrated that αSyn can initiate tau aggregation, while tau can accelerate the fibrillization and spread of αSyn [120– 122].”
-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila
Poças, G. M., Branco‐Santos, J., Herrera, F., Outeiro, T. F., & Domingos, P. M. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu606 · Cited by 38
Endo, R., Takashima, N., Nekooki-Machida, Y., Komi, Y., Hui, K. K., Takao, M., Akatsu, H., Murayama, S., Sawa, A., & Tanaka, M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.03.008 · Cited by 35
Clarimón, J., Molina‐Porcel, L., Gómez‐Isla, T., Blesa, R., Guardia‐Laguarta, C., González‐Neira, A., Estorch, M., Grau, J. M., Barraquer, L., Roig, C., et al. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181927577 · Cited by 36
Tau induces formation of α-synuclein filaments with distinct molecular conformations
Hojjatian, A., Dasari, A. K. R., Sengupta, U., Taylor, D. W., Daneshparvar, N., Yeganeh, F. A., Dillard, L. B., Michael, B. C., Griffin, R. G., Borgnia, M. J., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.03.091 · Cited by 41
Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Pirooznia, S. K., Rosenthal, L. S., Dawson, V. L., & Dawson, T. M. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000189 · Cited by 36
Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy
Giasson, B. I., Mabon, M. E., Duda, J. E., Montine, T. J., Robertson, D., Hurtig, H. I., Lee, V. M. ‐., & Trojanowski, J. Q. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0726-x · Cited by 35
Self-citationManca, M., Standke, H. G., Browne, D. F., Huntley, M. L., Thomas, O. R., Orru, C. D., Hughson, A. G., Kim, Y., Zhang, J., Tatsuoka, C. M., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02574-0 · Cited by 34
“Several studies have indicated that the co-occurrence of tau and α-synuclein (α-syn) aggregates can accelerate tau seeding processes in cellular and animal models [18, 23, 62].”
BackgroundBhasne, K., Sebastian, S., Jain, N., & Mukhopadhyay, S. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.04.020 · Cited by 33
The Role of Tau beyond Alzheimer’s Disease: A Narrative Review
Virgilio, E., Marchi, F. D., Contaldi, E., Dianzani, U., Cantello, R. M., Mazzini, L., & Comi, C. (2022) · Biomedicines · doi:10.3390/biomedicines10040760 · Cited by 32
“In neurodegenerative disorders, interactions between α-syn and Tau can promote protein fibrillization and stimulate the creation of pathological inclusions [100].”
BackgroundLiquid-liquid phase separation in Alzheimer’s disease
Fu, Q., Zhang, B., Chen, X., & Chu, L. (2024) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02407-3 · Cited by 33
“The phenomenon of αS and tau interacting and promoting the aggregation of each other has been observed long before [155, 156], but the underlying molecular mechanisms have not been revealed until recently. αS/tau condensates, possessing a multivalent complex network composed of weak interactions…”
Walker, L., Simpson, H., Thomas, A. J., & Attems, J. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01714-7 · Cited by 35
“It has been suggested that multiple pathologies promote suitable conditions for a synergistic relationship between proteins that results in cross seeding and exacerbation of overall pathology burden and accelerating cognitive decline [6, 13, 14, 21, 27].”
BackgroundMild cognitive impairment in Parkinson's disease: current view
Jellinger, K. A. (2024) · Frontiers in Cognition · doi:10.3389/fcogn.2024.1369538 · Cited by 40
Turk, F. E., Genst, E. D., Guilliams, T., Fauvet, B., Hejjaoui, M., Trani, J. M. D., Chiki, A., Mittermaier, A., Vendruscolo, M., Lashuel, H. A., et al. (2018) · Protein Science · doi:10.1002/pro.3412 · Cited by 32
Jellinger, K. A. (2022) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2022.05.024 · Cited by 34
Malgieri, G., & Grasso, G. (2013) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2013.10.008 · Cited by 33
Impairment of microtubule system increases α-synuclein aggregation and toxicity
Kim, M., Jung, W.-S., Lee, I., Bhak, G., Paik, S. R., & Hahn, J. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.020 · Cited by 33
Alpha‐synuclein in Parkinson's disease: Light from two new angles
Golbe, L. I., & Mouradian, M. M. (2004) · Annals of Neurology · doi:10.1002/ana.20036 · Cited by 33
Self-citationHeterotypic interactions in amyloid function and disease
Konstantoulea, K., Louros, N. N., Rousseau, F., & Schymkowitz, J. W. H. (2021) · FEBS Journal · doi:10.1111/febs.15719 · Cited by 34
A Combined Panel of Salivary Biomarkers in de novo Parkinson's Disease
Bartolo, M. I. D., Vivacqua, G., Belvisi, D., Mancinelli, R., Fabbrini, A., Manzo, N., Costanzo, M., Leodori, G., Conte, A., Fabbrini, G., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26550 · Cited by 32
“Tau and a-syn can enhance each other’s polymerization into fibrils.(14,15) Autophagy is essential for the removal of aggregated and misfolded proteins(36) and aggregation of both tau and a-syn is drastically increased by impaired autophagic-lysosomal degradation.”
BackgroundEarly‐onset Dementia with Lewy Bodies
Takao, M., Ghetti, B. F., Yoshida, H., Piccardo, P., Narain, Y., Murrell, J. R., Vidal, R., Glazier, B. S., Jakes, R., Tsutsui, M., et al. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00046.x · Cited by 33
Interaction of Myocilin with γ-Synuclein Affects Its Secretion and Aggregation
Surgucheva, I. G., Park, B., Yue, B. Y. J. T., Tomarev, S. I., & Surguchov, A. P. (2005) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-005-8471-4 · Cited by 32
Emerging pathways in genetic Parkinson’s disease: tangles, Lewy bodies and LRRK2
Devine, M. J., & Lewis, P. A. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06707.x · Cited by 30
Akbari, V., Ghobadi, S., Mohammadi, S., & Khodarahmi, R. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108218 · Cited by 33
Gadhave, K., Gehi, B. R., Kumar, P., Xue, B., Uversky, V. N., & Giri, R. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03414-9 · Cited by 35
Alpha-Synuclein deficiency ameliorates chronic methamphetamine induced neurodegeneration in mice
Ding, J., Hu, S., Meng, Y., Li, C., Huang, J. A., He, Y., & Qiu, P. (2020) · Toxicology · doi:10.1016/j.tox.2020.152461 · Cited by 31
New insights into atypical parkinsonism
Wenning, G. K., Krismer, F., & Poewe, W. H. (2011) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283480569 · Cited by 32
Benussi, L., Ghidoni, R., Paterlini, A., Nicosia, F. M., Alberici, A., Signorini, S. G., Barbiero, L., & Binetti, G. G. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.04.021 · Cited by 31
A Tangled Web – Tau and Sporadic Parkinson's Disease
Wray, S., & Lewis, P. A. (2010) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2010.00150 · Cited by 31
“In vitro work has shown that α-synuclein and tau are able to influence each other’s polymerization, and diffuse tau pathology is observed in transgenic mice expressing the α-synuclein A53T mutation (Giasson et al., 2003).”
BackgroundXiang, S., Kulminskaya, N., Habenstein, B., Biernat, J., Tepper, K., Paulat, M., Griesinger, C., Becker, S., Lange, A., Mandelkow�, E., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.6b09619 · Cited by 31
Seed-Induced Heterogeneous Cross-Seeding Self-Assembly of Human and Rat Islet Polypeptides
Hu, R., Ren, B., Zhang, M., Chen, H., Liu, Y., Liu, L., Gong, X., Jiang, B., Ma, J., & Zheng, J. (2017) · ACS Omega · doi:10.1021/acsomega.6b00559 · Cited by 31
Chiti, F. (2007) · Springer eBooks · doi:10.1007/0-387-25919-8_3 · Cited by 33
Selective neuronal vulnerability in Alzheimer’s disease: a network-based analysisPreprint
Roussarie, J.-P., Yao, V., Plautz, Z., Kasturia, S. E., Albornoz, C. A., Schmidt, E. F., Brichta, L., Barnea-Cramer, A. O., Heintz, N., Hof, P. R., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/499897 · Cited by 31
“For example, tau and a-synuclein have been described previously to influence each other’s aggregation into pathological lesions in Parkinson’s disease as well as in mice overexpressing these genes (Emmer et al., 2011; Giasson et al., 2003; Khandelwal et al., 2010, 2012).”
Ramezani, M., Wagenknecht-Wiesner, A., Wang, T., Holowka, D. A., Eliezer, D., & Baird, B. A. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00578-x · Cited by 33
Chen, Y., Wei, Q., Ou, R., Cao, B., Chen, X., Zhao, B., Guo, X., Yang, Y., Chen, K., Wu, Y., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133776 · Cited by 30
“α-synuclein is a primary protein component of LBs, and it is involved in the common mechanisms of α-synuclein and tau aggregation [20].”
BackgroundImmunotherapy Targeting Neurodegenerative Proteinopathies: α-Synucleinopathies and Tauopathies
Shin, J. H., Kim, H., & Jeon, B. (2019) · Journal of Movement Disorders · doi:10.14802/jmd.19057 · Cited by 31
Sierra, M., Gelpí, E., Martı́, M. J., & Compta, Y. (2016) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12308 · Cited by 30
α-Synuclein Aggregation and Modulating Factors
Paleologou, K. E., & El‐Agnaf, O. M. A. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-5416-4_6 · Cited by 33
“Transgenic mice that co-express α-syn and tau develop thioflavin S positive inclusions much faster compared to single transgenic mice, also suggesting that interactions between the two proteins can facilitate their aggregation and promote the formation of pathological inclusions (Giasson et al. 2003).”
BackgroundThe impact of genetic research on our understanding of Parkinson’s disease
Martin, I., Dawson, V. L., & Dawson, T. M. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)83002-x · Cited by 32
“Lastly, the interaction of a-synuclein with other amyloidogenic proteins such as tau (Giasson et al., 2003) or amyloid-b (Masliah et al.”
BackgroundNeuropathology of Parkinson’s Disease
Jellinger, K. A. (2014) · Springer eBooks · doi:10.1007/978-3-319-08046-8_2 · Cited by 31
Commentary: DLB and PDD: the same or different? Is there a debate?
McKeith, I. G. (2009) · International Psychogeriatrics · doi:10.1017/s1041610208008624 · Cited by 30
Mandler, M., Rockenstein, E. M., Overk, C., Mante, M., Florio, J. B., Adame, A., Kim, C., Santic, R., Schneeberger, A., Mattner, F., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.02.002 · Cited by 29
Rajendran, R., Raghavan, R. P., Al-Sehemi, A. G., Uddin, M. S., Aleya, L., & Mathew, B. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-17931-3 · Cited by 29
“Surprisingly, Aβ has been shown to stimulate tau accumulation, and the C-terminus of α-syn has been shown to interact with Tau under abnormal circumstances (Giasson et al. 2003).”
BackgroundReassessment of Neuronal Tau Distribution in Adult Human Brain and Implications for Tau Pathobiology
Paterno, G., Bell, B. M., Gorion, K.-M. M., Prokop, S., & Giasson, B. I. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01394-9 · Cited by 30
Self-citationConformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein
Sidhu, A., Segers‐Nolten, I. M. J., & Subramaniam, V. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00322 · Cited by 30
Guttuso, T. J., Andrzejewski, K. L., Lichter, D. G., & Andersen, J. K. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.05.016 · Cited by 29
Belur, N. R., Bustos, B. I., Lubbe, S. J., & Mazzulli, J. R. (2024) · Neuron · doi:10.1016/j.neuron.2024.05.003 · Cited by 28
Association Studies of Sporadic Parkinson’s Disease in the Genomic Era
Labbé, C., & Ross, O. A. (2014) · Current Genomics · doi:10.2174/1389202914666131210212745 · Cited by 30
Daniele, S., Pietrobono, D., Fusi, J., Gerfo, A. L., Cerri, E., Chico, L., Iofrida, C., Petrozzi, L., Baldacci, F., Giacomelli, C., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00017 · Cited by 28
“…to co-localize with tau and A β in platelets, as previously demonstrated in neurons or in cultured cells (Jensen et al., 1998; Masliah et al., 2001; Giasson et al., 2003; Lee et al., 2004; Mandal et al., 2006; Tsigelny et al., 2008; Badiola et al., 2011) and in RBCs (Daniele et al., 2017).”
Role of cellular prion protein in interneuronal amyloid transmission
del Rı́o, J. A., Ferrer, I., & Gavı́n, R. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.03.001 · Cited by 30
Vaikath, N. N., Erskine, D., Morris, C. M., Majbour, N. K., Vekrellis, K., Li, J., & El‐Agnaf, O. M. A. (2018) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12531 · Cited by 28
Alexandris, A. S., Walker, L., Liu, A. K. L., McAleese, K. E., Johnson, M., Pearce, R. K. B., Gentleman, S., & Attems, J. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12577 · Cited by 28
Negrini, M., Tomasello, G., Davidsson, M., Fenyi, A., Adant, C., Hauser, S., Espa, E., Gubinelli, F., Manfredsson, F. P., Melki, R., et al. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-212555 · Cited by 27
Louros, N., Ramakers, M., Michiels, E., Konstantoulea, K., Morelli, C., Garcia, T., Moonen, N., D’Haeyer, S., Goossens, V., Thal, D. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28955-9 · Cited by 28
Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies
Just, M. K., Gram, H., Theologidis, V., Jensen, P. H., Nilsson, K. P. R., Lindgren, M., Knudsen, K., Borghammer, P., & Berge, N. V. D. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.907293 · Cited by 32
“In vivo and in vitro studies have demonstrated that cross seeding of asyn, tau and Aβ is possible (Götz et al., 2001; Giasson et al., 2003; Guo et al., 2013; Williams et al., 2020).”
BackgroundFormation of toxic oligomers of polyQ-expanded Huntingtin by prion-mediated cross-seeding
Gropp, M., Klaips, C. L., & Hartl, F. U. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.09.031 · Cited by 28
Insoluble cellular prion protein and its association with prion and Alzheimer diseases
Zou, W., Zhou, X., Yuan, J., & Xiao, X. (2011) · Prion · doi:10.4161/pri.5.3.16894 · Cited by 28
Multi-Pronged Interactions Underlie Inhibition of α-Synuclein Aggregation by β-Synuclein
Williams, J. K., Yang, X., Atieh, T. B., Olson, M. P., Khare, S. D., & Baum, J. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.024 · Cited by 27
“The importance of determining the sequence regions that mediate protein-protein interactions has been highlighted in other investigations of the islet-amyloid polypeptide (IAPP) [63–66], β2-microglobulin [67, 68], and tau and Αβ peptides from Alzheimer’s disease [66, 69, 70], where co-polymerization between distinct s…”
BackgroundMa, L., Cao, T. T., Kandpal, G., Warren, L., Hess, J. F., Seabrook, G. R., & Ray, W. J. (2009) · Neurochemical Research · doi:10.1007/s11064-009-0038-1 · Cited by 27
Baiardi, S., Hansson, O., Levin, J., & Parchi, P. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14039 · Cited by 27
How to bake a brain: yeast as a model neuron
Sarto‐Jackson, I., & Tomáška, Ľ. (2016) · Current Genetics · doi:10.1007/s00294-015-0554-2 · Cited by 29
High discriminatory ability of peripheral and CFSF biomarkers in Lewy body diseases
Bougea, A. M., Stefanis, L., Emmanouilidou, E., Vekrelis, K., & Kapaki, E. N. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-019-02137-2 · Cited by 27
Macromolecular Structures and Proteins Interacting with the Microtubule Associated Tau Protein
Jiménez, J. S. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.05.023 · Cited by 28
Neurotoxic dopamine quinone facilitates the assembly of tau into fibrillar polymers
Santa‐María, I., Hernández, F., Smith, M. A., Perry, G. L., Ávila, J., & Moreno, F. J. (2005) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-7499-6 · Cited by 27
“In a rare familial Parkinson’s disease [34, 35], the concurrence of α-synuclein and tau aggregates can be the result of the action of oxidized products of dopamine.”
BackgroundThe effect of α-synuclein and Tau in methamphetamine induced neurotoxicity in vivo and in vitro
Ding, J., Lian, Y., Meng, Y., He, Y., Fan, H., Li, C., & Qiu, P. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.11.028 · Cited by 26
In Search of Effective Treatments Targeting α-Synuclein Toxicity in Synucleinopathies: Pros and Cons
Fouka, M., Mavroeidi, P., Tsaka, G., & Xilouri, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.559791 · Cited by 27
Jin, M., Wang, S., Gao, X., Zou, Z., Hirotsune, S., & Sun, L. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.382231 · Cited by 27
“The negatively charged C-terminus of αSyn directly interacts with the MT binding region of tau that synergistically promotes the aggregation and fibrillization of each other (Jensen et al., 1999; Giasson et al., 2003; Lu et al., 2020; Yan et al., 2020; Pan et al., 2022).”
BackgroundSutherland, G. T., Siebert, G. A., Kril, J. J., & Mellick, G. D. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110026 · Cited by 26
“In vivo interactions between tau and -synuclein are seen in double transgenic mice [96] and are supported by genetic studies [97].”
BackgroundBiernacka, J. M., Armasu, S. M., Cunningham, J. M., Ahlskog, J. E., Chung, S. J., & Maraganore, D. M. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.07.001 · Cited by 26
“It has been shown that MAPT induces fibrillization of alphasynuclein[12]; such fibrillization is proposed to be an initial step in the generation of PDpathogenic alpha-synuclein aggregates.”
BackgroundVidal-Martínez, G., Segura‐Ulate, I., Yang, B. C., Diaz-Pacheco, V., Barragan, J. A., Esquivel, J. D.-L., Chaparro, S. A., Vargas‐Medrano, J., & Perez, R. G. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113120 · Cited by 26
Familial associations of Alzheimer disease and essential tremor with Parkinson disease
Costello, S., Bordelon, Y. M., Bronstein, J. M., & Ritz, B. R. (2010) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.02974.x · Cited by 26
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
