线粒体动力学失衡和环境神经毒物对阿尔茨海默病病理进程影响的研究进展

Progress in effect of imbalance of mitochondrial dynamics and environmental neurotoxicants on Alzheimer disease pathology

线粒体动力学指细胞中的线粒体不断进行分裂融合的一种动态变化,是维持胞内物质与能量运输的重要保障,发动蛋白相关GTP酶1、Fis1、线粒体分裂因子、线粒体融合蛋白1/2和视神经萎缩蛋白1等蛋白为这一过程的直接参与者,它们受到磷酸化、S-亚硝基化、泛素化、小泛素化和蛋白酶解等信号的精密调控。神经细胞的突触形态与功能维持极度依赖线粒体正常分布与功能,而体内外神经毒性物质可能通过干扰线粒体动力学平衡引发神经元能量代谢障碍,活性氧释放增多,并可加速细胞凋亡。越来越多研究表明,线粒体动力学失衡是阿尔兹海默综合征早期病理进程中的关键事件之一。

Mitochondrial dynamics refers to the morphological changes of mitochondria undergoing continuous fission and fusion. Dynamin related GTPase 1, Fisl, mitochondrial fission factor, mitofusin 1/2, and optic atrophy protein 1 have been found to play key roles in this process. They are subject to upstream regulations including phosphorylation, S-ni- trosylation, ubiquitination, sumoylation and proteolysis. Normal mitochondrial functioning is an indispensible part of the maintenance of synapses morphology and function. Neurotoxicants may affect mitochondrial dynamics and then result in the dysfunction of oxidative phosphorylation and increas reactive oxygen species production and neuron apoptosis. More and more researches suggest that the imbalance of mitochondrial dynamics is a key pathological event in the early stage of Alzheimer disease.