帕金森病遗传学和病理生理学。

IF 12.1 1区医学 Q1 NEUROSCIENCES

Annual review of neuroscience Pub Date : 2021-07-08 DOI:10.1146/annurev-neuro-100720-034518

Gabriel E Vázquez-Vélez, Huda Y Zoghbi

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引用次数: 67

摘要

帕金森病(PD)是一种常见的神经退行性疾病，以黑质致密部变性和路易小体α-突触核蛋白积累为特征。帕金森病是由环境因素和遗传变异共同引起的。这些变异的范围从高渗透的孟德尔等位基因到仅适度增加疾病风险的等位基因。在这里，我们回顾了关于帕金森病的遗传学知识。我们还描述了PD遗传学如何巩固了内体、溶酶体和线粒体功能障碍在PD病理生理学中的作用。最后，我们强调了这三种途径如何受到α-突触核蛋白的影响，以及如何利用这些知识开发疾病修饰疗法。

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Parkinson's Disease Genetics and Pathophysiology.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

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来源期刊

Annual review of neuroscience 医学-神经科学

CiteScore

25.30

自引率

0.70%

发文量

期刊介绍： The Annual Review of Neuroscience is a well-established and comprehensive journal in the field of neuroscience, with a rich history and a commitment to open access and scholarly communication. The journal has been in publication since 1978, providing a long-standing source of authoritative reviews in neuroscience. The Annual Review of Neuroscience encompasses a wide range of topics within neuroscience, including but not limited to: Molecular and cellular neuroscience, Neurogenetics, Developmental neuroscience, Neural plasticity and repair, Systems neuroscience, Cognitive neuroscience, Behavioral neuroscience, Neurobiology of disease. Occasionally, the journal also features reviews on the history of neuroscience and ethical considerations within the field.