邻苯三酚靶向调控α-突触核蛋白聚集的功能

打开文本图片集

中图分类号：R93 文献标志码：A

Abstract：To investigate the molecular mechanism bywhich the small molecule compound pyrogallol（PYG）targetedly regulates the aggregation of α -synuclein （α∝-syn） ），as well as its potential in treating Parkinson disease，the inhibitory effect of PYG on α -syn nucleation and aggregation was evaluated using thioflavin T（ThT） fluorescence assays. Images obtained bytransmission electron microscopyand circular dichroism spectra wereemployed to analyze conformational changes.Inaddition，in vitrocellexperiments were conducted toexamine the impactof PYGon neuronal membrane damage and cell viability induced by α -syn aggregates. The results show that PYG significantly inhibits ∝- syn nucleation and aggregation in a concentration-dependent manner，disrupts β- sheet structures to depolymerize mature fibrils，and transforms theminto amorphousaggregates，therebyreducing cytotoxicity.In vitroexperimental results confirm that PYG can alleviate α∝-syn aggregates-induced neuronal membrane damage and recover cell viability. However，highconcentration PYG exhibits cytotoxicitywhen used to treat cells alone.

Keywords ： Parkinson disease; α -synuclein；pyrogallol；nerve cell toxicity

帕金森病（Parkinsondisease，PD）是发病率仅次于阿尔茨海默病（Alzheimerdisease，AD）的神经退行性疾病，PD患者早期常出现感觉障碍、心理认知障碍和自主神经功能障碍，随后伴有一系列与运动相关症状，如静息性震颤、肌肉僵硬、运动障碍等，全球 65岁以上人群的发病率为 2%～3%[1] 。（剩余14775字）