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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid / chemistry
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Amyloid / metabolism
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Animals
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Biopolymers
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Brain Chemistry*
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Humans
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Electron
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Microscopy, Fluorescence
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Microscopy, Immunoelectron
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / metabolism
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Neurodegenerative Diseases / metabolism
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Neurons / chemistry
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Oligodendroglia / chemistry
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Protein Conformation
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Synucleins
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Tauopathies / metabolism
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alpha-Synuclein
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tau Proteins / analysis
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tau Proteins / chemistry*
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tau Proteins / metabolism
Substances
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Amyloid
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Biopolymers
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Nerve Tissue Proteins
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Protein Isoforms
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SNCA protein, human
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Snca protein, mouse
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Synucleins
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alpha-Synuclein
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tau Proteins