Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.
Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.
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DOI：
10.1016/j.pharmthera.2015.10.005
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发表时间：
2015-12
影响因子：
13.5
通讯作者：
Hausenloy DJ
中科院分区：
文献类型：
--
作者：
Mukherjee UA;Ong SB;Ong SG;Hausenloy DJ
缺血性心脏病（IHD）是全球死亡和残疾的主要原因。因此，需要用于保护心脏免受急性缺血/再灌注损伤（IRI）的新的治疗靶点以减轻心肌细胞死亡，保护心肌功能，并防止心力衰竭的发作。在这方面，一组特定的线粒体蛋白，这已被链接到帕金森氏病（PD）的家族形式，可能提供新的治疗目标，心脏保护。在黑质多巴胺能神经元中，这些PD蛋白，包括Parkin、PINK 1、DJ-1、LRRK 2和α-突触核蛋白，通过维持正常线粒体功能、保护免受氧化应激、介导线粒体自噬和防止细胞凋亡，在防止细胞死亡中发挥重要作用。因此，这些罕见的家族性PD可能为线粒体功能障碍和PD发展的病理生理学提供重要的见解。有趣的是，这些PD蛋白也存在于心脏中，但它们在心肌健康和疾病中的作用尚不清楚。在这篇文章中，我们回顾了这些PD蛋白在心脏中的作用，并探讨了它们作为心脏保护的新型线粒体靶点的潜力。
Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death—through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.