Formation of aberrant phosphotau fibrillar polymers in neural cultured cells.
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.
Pérez
Mar
M
Centro de Biología Molecular (CSIC/UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Hernández
Félix
F
Gómez-Ramos
Alberto
A
Smith
Mark
M
Perry
George
G
Avila
Jesús
J
D000447:Aldehydes / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000737:chemistry; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
D000447:Aldehydes; D011108:Polymers; D016875:tau Proteins; D019319:Okadaic Acid; C027576:4-hydroxy-2-nonenal