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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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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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