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科学家发现Miro1蛋白在帕金森病治疗中的作用
作者:小柯机器人 发布时间:2019/9/29 14:12:17

美国斯坦福大学医学院Xinnan Wang研究小组的一项最新研究发现Miro1蛋白能够标记帕金森病(PD)亚型,并且减少Miro1能够挽救帕金森模型中神经元的丢失。相关论文2019年9月26日在线发表在《细胞—代谢》杂志上。

研究人员测试了在检测PD和评估潜在的治疗方法方面Miro1的临床效用。来自不同PD患者的皮肤成纤维细胞中,研究人员使用生化分析测量了Miro1对线粒体去极化的反应,发现超过94%的患者成纤维细胞细胞系在去极化后未能去除Miro1。研究人员鉴定了一个小分子,可以修复PD成纤维细胞中Miro1的这种缺陷。用这种化合物治疗患者来源的神经元和果蝇模型可以挽救运动缺陷以及多巴胺能神经的退行性改变。

这些结果表明,跟踪这种Miro1标记并研发基于Miro1的疗法可能会为个性化医学开辟新途径。

研究人员表示,鉴定PD的分子靶标和药动力学标志物将使临床治疗和实验疗法更加有效。Miro1蛋白位于线粒体表面并介导线粒体的运动。从去极化的线粒体中除去Miro1,能够促进其通过线粒体自噬而清除。

附:英文原文

Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models

Author: Chung-Han Hsieh, Li Li, Roeland Vanhauwaert, Kong T. Nguyen, Mary D. Davis, Guojun Bu, Zbigniew K. Wszolek, Xinnan Wang

Issue&Volume: 26 September 2019

Abstract: 

The identification of molecular targets and pharmacodynamic markers for Parkinson’s disease (PD) will empower more effective clinical management and experimental therapies. Miro1 is localized on the mitochondrial surface and mediates mitochondrial motility. Miro1 is removed from depolarized mitochondria to facilitate their clearance via mitophagy. Here, we explore the clinical utility of Miro1 for detecting PD and for gauging potential treatments. We measure the Miro1 response to mitochondrial depolarization using biochemical assays in skin fibroblasts from a broad spectrum of PD patients and discover that more than 94% of the patients’ fibroblast cell lines fail to remove Miro1 following depolarization. We identify a small molecule that can repair this defect of Miro1 in PD fibroblasts. Treating patient-derived neurons and fly models with this compound rescues the locomotor deficits and dopaminergic neurodegeneration. Our results indicate that tracking this Miro1 marker and engaging in Miro1-based therapies could open new avenues to personalized medicine.

DOI: 10.1016/j.cmet.2019.08.023

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30497-8

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx