期刊
EUROPEAN JOURNAL OF BIOCHEMISTRY
卷 269, 期 5, 页码 1484-1489出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1432-1033.2002.02794.x
关键词
Alzheimer's disease; tauopathies; oxidative stress; tau phosphorylation; aberrant aggregates
Here we show. for the first time. the in vitro formation of filamentous aggregates of phosphorylated tau protein in SH-SY5Y human neuroblastoma cells. The formation of such aberrant aggregates, similar to those occurring in vivo in Alzheimer's disease and other tauopathies, requires okadaic acid, a phosphatase inhibitor, to increase the level of phosphorylated tau, and hydroxynonenal, a product of oxidative stress that selectively adducts and modifies phosphorylated tau. Our findings suggest that both phosphorylation and oxidative modification are required for tau filament formation. Importantly, the in vitro formation of intracellular tau aggregates could be used as a model of tau polymerization and facilitate the development of novel therapeutic approaches.
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