Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer's disease.
Aggregation of microtubule-associated protein tau into insoluble intracellular neurofibrillary tangles is a characteristic hallmark of Alzheimer's disease (AD) and other neurodegenerative diseases, including progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, frontotemporal dementias with Parkinsonism linked to chromosome 17, and Pick's disease. Tau is abnormally hyperphosphorylated in AD and aberrant tau phosphorylation contributes to the neuropathology of AD and other tauopathies. Anti-aggregation and anti-phosphorylation are main approaches for tau-based therapy. In this study, we report that a select grape-seed polyphenol extract (GSPE) could potently interfere with the assembly of tau peptides into neurotoxic aggregates. Moreover, oral administration of GSPE significantly attenuated the development of AD type tau neuropathology in the brain of TMHT mouse model of AD through mechanisms associated with attenuation of extracellular signal-receptor kinase 1/2 signaling in the brain.
Wang
Jun
J
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Santa-Maria
Ismael
I
Ho
Lap
L
Ksiezak-Reding
Hanna
H
Ono
Kenjiro
K
Teplow
David B
DB
Pasinetti
Giulio Maria
GM
D000544:Alzheimer Disease / Q000150:complications; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D016874:Neurofibrillary Tangles / Q000473:pathology / Q000648:ultrastructure; D010636:Phenols / Q000627:therapeutic use*; D008517:Phytotherapy / Q000379:methods*; D059808:Polyphenols; D012639:Seeds / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013057:Spectrum Analysis; D024801:Tauopathies / Q000188:drug therapy* / Q000209:etiology; D027843:Vitis; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D016875:tau Proteins