α7-nAChR在β-淀粉样蛋白诱导神经元超兴奋及神经毒性中的新机制研究

一般认为，阿尔茨海默病（AD）主要是由β淀粉样蛋白（Aβ）引起的病变，但其神经毒性机制尚不明白。研究提示，Aβ过量表达并积聚可影响神经元兴奋性，而这也正可能是导致AD认知功能障碍的主要上游机制。基于我们前期工作提示：长期Aβ处理可引起神经元超兴奋，并且可上调α7-nAChR的水平。本项目主要采用电生理学、细胞分子生物学等实验手段，来研究长期Aβ处理是否诱导神经元超兴奋和对α7-nAChR调控的作用及相关机制，以及α7-nAChR如何参与Aβ引起神经元超兴奋及神经毒性的作用机制。通过本研究来揭示Aβ发挥神经毒性作用的可能机制，为探寻AD早期认知功能障碍机制提供思路和线索，进而为消除AD发生发展的治疗新策略提供实验依据。

Generally speaking, it is believed that amyloid beta (Aβ) protein plays an important role on Alzheimer's disease (AD). However, the neurotoxic mechanism is not yet clear. The study shows that the Aβ-induced neuronal hyperexcitation may be caused by the accumulation of Aβ and be also the upstream mechanism in cognitive deficits of AD. Based on the hints of the preliminary work, chronic exposure of the Aβ can induce neuronal hyperexcitability and the upregulation of α7-nAChR. In this project, using electrophysiology, cell and molecular biology, and other experimental techniques, we will testify the neuronal excitation and the regulation of α7-nAChR induced by the chronic exposure of Aβ and their mechanisms, explore the function and mechanisms how α7-nAChR is involved in Aβ induced neuronal hyperexcitation and neurotoxicity. The proposed project is to explore the possible mechanism of Aβ induced neurotoxicity, which can provide new clue to explore the cognitive deficits in the early AD and the evidence for new treatment strategy to eliminate the AD development and progression.