帕金森病的线粒体功能障碍。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY
Journal of Neural Transmission Pub Date : 2024-12-01 Epub Date: 2024-11-25 DOI:10.1007/s00702-024-02863-2
Nobutaka Hattori, Shigeto Sato
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引用次数: 0

摘要

帕金森病(PD)黑质细胞死亡的确切原因仍不清楚。然而,对 MPTP 诱导的实验性帕金森病的研究大大推进了我们的认识。在这一模型中,人们普遍认为线粒体呼吸衰竭是细胞死亡的主要机制。研究表明,MPTP 的毒性代谢产物会抑制线粒体中复合体 I 和 α-酮戊二酸脱氢酶的活性。此后,许多研究小组开始关注帕金森病的线粒体功能障碍,并在帕金森病患者的大脑、骨骼肌和血小板中发现了复合体 I 或 III 的缺陷。关于外周器官线粒体功能的衰退还存在一些争论。然而,由于路易体的主要组成蛋白α-突触核蛋白在外周器官中积累,因此将帕金森病视为一种全身性疾病是合理的。此外,在帕金森氏症患者的大脑中还发现了缺失 4,977 个碱基对的突变线粒体 DNA,这表明与年龄相关的缺失 mtDNA 在纹状体中加速积累,并可能导致帕金森氏症的病理生理学。虽然帕金森病的病因尚不清楚,但线粒体功能障碍无疑是导致帕金森病细胞死亡的一个因素。此外,家族性帕金森病的致病基因 parkin(现为 PRKN)和 PTEN 诱导的假定激酶 1(PINK1)这两种基因的产物也参与了线粒体的质量控制。此外,我们还成功分离并鉴定了参与线粒体电子传递系统的 CHCHD2。毫无疑问,线粒体功能障碍是导致帕金森病细胞死亡的原因之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial dysfunction in Parkinson's disease.

The exact cause of nigral cell death in Parkinson's disease (PD) is still unknown. However, research on MPTP-induced experimental parkinsonism has significantly advanced our understanding. In this model, it is widely accepted that mitochondrial respiratory failure is the primary mechanism of cell death. Studies have shown that a toxic metabolite of MPTP inhibits Complex I and alpha-ketoglutarate dehydrogenase activities in mitochondria. Since then, many research groups have focused on mitochondrial dysfunction in PD, identifying deficiencies in Complex I or III in PD patients' brains, skeletal muscle, and platelets. There is some debate about the decline in mitochondrial function in peripheral organs. However, since α-synuclein, the main component protein of Lewy bodies, accumulates in peripheral organs, it is reasonable to consider PD a systemic disease. Additionally, mutant mitochondrial DNA with a 4,977 base pair deletion has been found in the brains of PD patients, suggesting that age-related accumulation of deleted mtDNA is accelerated in the striatum and may contribute to the pathophysiology of PD. While the cause of PD remains unknown, mitochondrial dysfunction is undoubtedly a factor in cell death in PD. In addition, the causative gene for familial PD, parkin (now PRKN), and PTEN-induced putative kinase 1 (PINK1), both gene products are also involved in mitochondrial quality control. Moreover, we have successfully isolated and identified CHCHD2, which is involved in the mitochondrial electron transfer system. There is no doubt that mitochondrial dysfunction contributes to cell death in PD.

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来源期刊
Journal of Neural Transmission
Journal of Neural Transmission 医学-临床神经学
CiteScore
7.20
自引率
3.00%
发文量
112
审稿时长
2 months
期刊介绍: The investigation of basic mechanisms involved in the pathogenesis of neurological and psychiatric disorders has undoubtedly deepened our knowledge of these types of disorders. The impact of basic neurosciences on the understanding of the pathophysiology of the brain will further increase due to important developments such as the emergence of more specific psychoactive compounds and new technologies. The Journal of Neural Transmission aims to establish an interface between basic sciences and clinical neurology and psychiatry. It intends to put a special emphasis on translational publications of the newest developments in the field from all disciplines of the neural sciences that relate to a better understanding and treatment of neurological and psychiatric disorders.
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