帕金森病重要致病基因致线粒体功能损伤的机制研究进展

The mechanisms of mitochondrial dysfunction caused by pathogenic genes of Parkinson′s disease

帕金森病是一种严重危害中老年人健康、以黑质-纹状体多巴胺能神经元退行性损伤为主要病理特征的神经退行性疾病。由于其影响因素众多、致病的生物学机制复杂,截至目前临床仍缺乏针对帕金森病的有效治疗手段,相关研究一直是该领域的热点。近年来,多数关于帕金森病的报道共同提示其发生发展与线粒体功能损伤有关,而线粒体功能损伤常常受到复杂基因调控的影响。全基因组关联研究证明,单基因帕金森病基因位点与线粒体功能损伤相关。关于帕金森病致病基因如何调控线粒体功能损伤,进而影响神经元生理功能,最终导致帕金森病发生,目前各类研究尚无统一认识。文中围绕帕金森病重要致病基因致线粒体功能损伤的生物学机制,对既往的相关研究进行综述,以求为帕金森病致病机制的研究提示方向,也为帕金森病的线粒体靶向治疗策略的开发提供理论基础。

Parkinson′s disease(PD)is a complex neurodegenerative disorder typically known for characteristic loss of dopaminergic neurons in the substantia nigra striatum.To date,therapeutic approaches for PD are still lacking due to the multifactorial etiology and complicated pathogenesis.Thus,the studies relative to the biological mechanisms and drug development of PD are the hotspot in this field.In recent years,numerous studies suggest that the PD is associated with mitochondrial dysfunction which is affected by multiple genes regulation.Genome-wide association studies have proved that monogenic PD gene locus is associated with mitochondrial dysfunction.Although there are many studies on how PD pathogenic genes regulate mitochondrial dysfunction then affect neuronal physiological function and ultimately lead to the PD,the effects of mutations in PD-associated genes on mitochondrial dysfunction remain not fully understood.In this review,the literature discussing the mechanisms of mitochondrial dysfunction in the context of PD was summarized with the aim to implicate the potential opportunities for therapeutically targeting mitochondria.