Tau蛋白在阿尔茨海默病中对线粒体的影响

Effects of Tau Protein on Mitochondrial Function in Alzheimer's Disease

Tau蛋白是一种重要的蛋白质,在生理上促进微管的组装和稳定,并参与神经元发育、轴突运输和神经元极性。在阿尔茨海默病(Alzheimer's disease,AD)中,Tau蛋白经历了病理修饰,其中可溶性Tau组装成不可溶性的细丝,导致突触失效和神经退行性病变。线粒体是神经元中最重要的细胞器,是主要的能量来源,通过氧化磷酸化提供三磷酸腺苷(adenosine triphosphate,ATP),维持正常的神经元稳态和功能。越来越多的证据表明,线粒体功能障碍在AD的发病机制中起着关键作用。对神经元中的线粒体生物能学、转运和形态产生负面影响,导致AD的突触损伤和认知能力下降。Tau蛋白被证明与线粒体蛋白相互作用,损害线粒体动力学、线粒体的形态和自噬,导致神经毒性。该文就Tau蛋白对线粒体的影响在AD的损伤作用以及机制作一综述。

Tau protein is an important protein that physiologically promotes microtubule assembly and stabilization and is involved in neuronal development,axonal transport and neuronal polarity.In Alzheimer's disease(AD),Tau proteins undergo pathological modifications in which soluble Tau assembles into insoluble filaments,leading to synaptic failure and neurodegenerative lesions.Mitochondria are the most important organelles in neurons and are the main source of energy,providing adenosine triphosphate(ATP)through oxidative phosphorylation to maintain normal neuronal homeostasis and function.A growing body of evidence suggests that mitochondrial dysfunction plays a key role in the pathogenesis of AD.Negative effects on mitochondrial bioenergetics,transport and morphology in neurons lead to synaptic damage and cognitive decline in AD.Tau proteins have been shown to interact with mitochondrial proteins,impairing mitochondrial dynamics,mitochondrial morphology and autophagy,leading to neurotoxicity.This article provides a review of the effects of Tau proteins on mitochondria in AD and the mechanisms of action.