Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

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Sci. Aging Knowl. Environ., 7 May 2003
Vol. 2003, Issue 18, p. or6

OTHER RESOURCES

Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

Benoit I. Giasson, Mark S. Forman, Makoto Higuchi, Lawrence I. Golbe, Charles L. Graves, Paul T. Kotzbauer, John Q. Trojanowski, and Virginia M.-Y. Lee

http://sageke.sciencemag.org/cgi/content/abstract/sageke;2003/18/or6

Abstract: Science 300, 636-640 (2003)

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.