Monday, November 25, 2019

Journal of Scientific and Technical Research - BJSTR Journal

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.


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