title: Formation of aberrant phosphotau fibrillar polymers in neural cultured cells.
abstract: 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.
authors.affiliation: Centro de Biología Molecular (CSIC/UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Pérez
authors.forename: Félix
authors.initials: F
authors.lastname: Hernández
authors.forename: Alberto
authors.initials: A
authors.lastname: Gómez-Ramos
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: 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
chemical_list: D000447:Aldehydes; D011108:Polymers; D016875:tau Proteins; D019319:Okadaic Acid; C027576:4-hydroxy-2-nonenal