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全球范围内帕金森病的遗传基础研究:从发现到临床应用。

Uncovering the genetic basis of Parkinson's disease globally: from discoveries to the clinic.

机构信息

Division of Neurology, Department of Medicine, and The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Division of Neurology, Department of Medicine, and The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Lancet Neurol. 2024 Dec;23(12):1267-1280. doi: 10.1016/S1474-4422(24)00378-8. Epub 2024 Oct 21.

Abstract

Knowledge on the genetic basis of Parkinson's disease has grown tremendously since the discovery of the first monogenic form, caused by a mutation in α-synuclein, and with the subsequent identification of multiple other causative genes and associated loci. Genetic studies provide insights into the phenotypic heterogeneity and global distribution of Parkinson's disease. By shedding light on the underlying biological mechanisms, genetics facilitates the identification of new biomarkers and therapeutic targets. Several clinical trials of genetics-informed therapies are ongoing or imminent. International programmes in populations who have been under-represented in Parkinson's disease genetics research are fostering collaboration and capacity-building, and have already generated novel findings. Many challenges remain for genetics research in these populations, but addressing them provides opportunities to obtain a more complete and equitable understanding of Parkinson's disease globally. These advances facilitate the integration of genetics into the clinic, to improve patient management and personalised medicine.

摘要

自首次发现由α-突触核蛋白突变引起的单基因形式的帕金森病以来,人们对帕金森病遗传基础的认识有了极大的提高,随后又确定了多个其他致病基因和相关基因座。遗传研究为了解帕金森病的表型异质性和全球分布提供了线索。通过揭示潜在的生物学机制,遗传学有助于确定新的生物标志物和治疗靶点。目前正在进行或即将进行几项基于遗传学的治疗临床试验。在帕金森病遗传学研究中代表性不足的人群中开展的国际计划正在促进合作和能力建设,并已取得新的发现。这些人群的遗传学研究仍面临许多挑战,但解决这些问题为全球更全面、更公平地了解帕金森病提供了机会。这些进展促进了遗传学在临床上的整合,以改善患者管理和个体化医疗。

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