The Function Of Binl In Alzheimer’s Disease

Alzheimer’s disease (AD) is a common neurodegenerative disease with the clinical manifestation of gradually decreasing on mentality and cognitive function, followed by progressive loss of action ability.The major pathological features of AD are extracellular senile plaques and intracellular neurofibrillary tangles. The former is composed of β-amyloid (Aβ) peptides, which are derived from its precursor protein App through sequential cleavages by (3-and y-secretases. The latter is composed of hyperphosphorylated tau protein. Hence, proteins which can regulate App cleavage and/or tau phosphorylation may become drug targets for AD therapy.Recent genome-wide association studies have identified the Bin1(bridging integrator1) gene as a major risk factor associated with late onset AD. However, although there are some reports suggesting that the level of Binl is altered in AD samples, the detailed mechanism underlying Bin1-mediated AD pathology remains elusive.In this study, we explored the molecular link between Bin1and AD. We first studied any level change of Bin1in AD and found that although not significantly different, the protein level of Bin1was decreased in AD brain samples compared with controls. Next, we found that overexpression of Bin1did not affect levels of App, α-, β-and y-secretases, but dramatically increased the phosphorylation of tau. Since oxidative stress is an important effector to AD, we also investigated possible involvement of Binl in oxidative stress. The results showed that H2O2treatments markedly increased Binl mRNA and protein levels. Moreover, downergulation of Bin1could alleviate H2O2-induced cell death.Taken together, our study suggests that Bin1participates in AD probably through increasing the phosphorylation and that Bin1may mediate oxidative stress-induced cell death. These results may strengthen our understanding of the molecular mechanism underying AD.