期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 22, 期 2, 页码 653-661出版社
IOS PRESS
DOI: 10.3233/JAD-2010-101074
关键词
Aggregation; Alzheimer's disease; hyperphosphorylation; neurofibrillary tangles; tauopathies
资金
- Department of Veterans Affairs, Veterans Health Administration
- Office of Research and Development and Biomedical Laboratory Research and Development at the James J. Peters Veteran Affairs Medical Center
- National Institute of Health [PO1AT004511, AG027818]
- CurePSP
- Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA
- NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE [P01AT004511] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG027818] Funding Source: NIH RePORTER
- Grants-in-Aid for Scientific Research [22790815] Funding Source: KAKEN
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.
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