Okadaic Acid Induces the Rats� Memory Impairment and Tau Protein Hyperphosphorylation And Intervened by Flavonoids from Stem and Leaf of Scutellaria Baicalensis Georgi
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 9, Issue 4
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. The neuropathology of AD is represented by widespread deposits of neurofibrillary tangles (NFTs) formed by phosphorylated tau (p-tau) protein and of senile plaques (SP) containing amyloid β (Aβ) protein. A series of epidemiological statistical results and the experimental study showed that solely SP cannot result in AD clinical dementia symptoms, while the formation and the number of NFTs is directly related to the occurrence of dementia. NTFs formation is due to excessive phosphorylated tau protein occurred after the formation of the structure of the double helix shape. Actually, tau, a microtubule-binding protein, primarily promotes microtubule stability and contains 2-3 phosphate groups per molecule in the normal brain. However, in the AD brain, tau protein hyperphosphorylated, containing 5-9 phosphate groups per molecule, has a decreased ability to combine with microtubules and dimerize. Stable tau dimers form tau oligomers, which continue aggregating to form subunits of filaments called protomers. Two protomers wound around each other form a paired helical filament (PHF), and excessive PHF assembly leads to NFTs and eventually AD [1]. An imbalance between tau phosphorylation and dephosphorylation is critical to AD tauopathy. Several protein kinases, including cyclin-dependent kinase 5 (CDK5), cyclic AMP- dependent protein kinase (PKA) and glycogen synthase kinase 3β (GSK3β) have been confirmed to phosphorylate tau protein at different sites, such as at serine (Ser) 199, Ser202, Ser262, Ser396, Ser214, Ser404, Thr231 and other sites of tau protein. These forms of p-tau protein are found in the AD brain. In addition, the phosphorylation of protein kinases at different sites can alter their kinase activity. For instance, GSK3β activity is inhibited by phosphorylation at serine (Ser) 9, and its activity is enhanced by phosphorylation at tyrosine (Tyr) 216. Hyperphosphorylated tau protein also results from the reduced activity of protein phosphatase (PP2A, PP2B, PP2C, PP1) that indicates a decisive role of PP in tangle formation in AD. Then any strategy that can maintain hyperphosorylation of tau protein can be used to establish an AD- like animal model for studying pathophysiology process and drug screen with AD [2].
Authors and Affiliations
Cheng Jianjun, Shang Yazhen
Keywords
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- EP ID EP591799
- DOI 10.26717/BJSTR.2018.09.001842
- Views 174
- Downloads 0
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