Current perspective of mitochondrial biology in Parkinson's disease.
Current perspective of mitochondrial biology in Parkinson's disease.
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DOI：
10.1016/j.neuint.2018.03.001
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发表时间：
2018-07
影响因子：
4.2
通讯作者：
Thomas B
中科院分区：
文献类型：
--
作者：
Ammal Kaidery N;Thomas B
帕金森病（PD）是最常见的神经退行性运动障碍之一，其特征是黑质致密部多巴胺能神经元的优先丧失和含有α-突触核蛋白的路易小体的存在。虽然帕金森氏病的病因仍然难以捉摸，但在了解帕金森氏病发病机制方面取得了显着进展。在过去的二十年里，发现的爆炸式增长导致了几个常染色体显性和隐性基因的鉴定，导致家族形式的帕金森病。这些家族性PD基因产物的研究为更常见的散发性PD的分子发病机制提供了重要的见解。越来越多的证据表明，帕金森病的病因是多因素的，涉及遗传和环境因素之间复杂的相互作用。来自人体组织、遗传和毒素诱导的动物和细胞模型的大量证据表明，线粒体功能障碍在帕金森病的病理生理中起着核心作用。生物能量学缺陷导致的线粒体功能缺陷、线粒体DNA的改变、活性氧的产生、钙稳态异常以及线粒体动力学和质量控制的异常都与帕金森病神经元细胞死亡的潜在机制有关。在这篇综述中，我们讨论了家族性PD相关基因和环境因素如何连接调节线粒体功能的途径，从而可能在线粒体完整性水平上融合家族性和散发性PD。我们还概述了针对帕金森病线粒体功能障碍的治疗策略的现状。揭示影响帕金森病线粒体稳态的潜在途径可能是治疗这种使人衰弱的神经退行性运动障碍的关键。
Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorder characterized by preferential loss of dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies containing α-synuclein. Although the cause of PD remains elusive, remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. An explosion of discoveries during the past two decades has led to the identification of several autosomal dominant and recessive genes that cause familial forms of PD. The investigations of these familial PD gene products have shed considerable insights into the molecular pathogenesis of the more common sporadic PD. A growing body of evidence suggests that the etiology of PD is multifactorial and involves a complex interplay between genetic and environmental factors. Substantial evidence from human tissues, genetic and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of PD. Deficits in mitochondrial functions due to bioenergetics defects, alterations in the mitochondrial DNA, generation of reactive oxygen species, aberrant calcium homeostasis, and anomalies in mitochondrial dynamics and quality control are implicated in the underlying mechanisms of neuronal cell death in PD. In this review, we discuss how familial PD-linked genes and environmental factors interface the pathways regulating mitochondrial functions and thereby potentially converge both familial and sporadic PD at the level of mitochondrial integrity. We also provide an overview of the status of therapeutic strategies targeting mitochondrial dysfunction in PD. Unraveling potential pathways that influence mitochondrial homeostasis in PD may hold the key to therapeutic intervention for this debilitating neurodegenerative movement disorder.
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DOI：
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发表时间：
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期刊：
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影响因子：
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