线粒体损伤相关的帕金森病分子机制及其药物靶标

Molecular Mechanisms and Drug Targets of Parkinson’s Disease Associated with Mitochondrial Damage

帕金森病(Parkinson’sdisease,PD)的主要病理特征是中脑黑质多巴胺能神经元的丢失,其疾病进程与年龄增长、环境毒物、家族遗传等诸多风险因素有关。大量研究表明,线粒体的损伤或功能障碍是多巴胺能神经元应答于多种致病因素,并引起神经元功能退化或死亡的重要病理事件。因此,解析线粒体损伤相关的PD分子机制有助于发现新的药物靶标和拓宽新药研发思路。并且,干预线粒体损伤相关的分子机制能够有效延缓疾病的发生和发展,是提高PD临床治疗效果和改善PD患者生活质量的重要途径。本文综述了目前较为新颖的有关线粒体损伤的PD分子机制,并讨论了由此衍生的可能药物靶标和候选药物,以期为PD的防治和新药研发提供新的理论依据。

The loss of dopaminergic neurons in the midbrain substantia nigra region is the main pathological feature of Parkinson’s disease. Many risk factors such as aging, environment toxicants and family genetics, is involed in the progress of Parkinson’s disease. Emerging studies have shown that damage or dysfunction of mitochondrial is an essential pathological event that dopaminergic neurons respond to a variety of pathogenic factors and cause the degradation or death of neurons. Therefore, analyze molecular mechanism of PD that related to mitochondrial damage is helpful to find new drug targets and broaden the pathway of new drug research and development. Moreover, the intervention of molecular mechanisms related to mitochondrial damage can effectively delay the occurrence and development of PD, which is an important way to improve the clinical treatment effect and improve the quality of life in patients with Parkinson’s disease. This review will focus on the novel molecular mechanism of PD related to mitochondrial damage, and discuss the potential drug targets and candidate drugs derived from this mechanism, in order to provide new theoretical basis for the prevention and treatment of PD and the development of new drugs.