Xia Ninuo, Cabin Deborah E, Fang Fang, Reijo Pera Renee A
Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
McLaughlin Research Institute for Biomedical Sciences, Inc., Great Falls, MT, United States.
Front Neurosci. 2022 May 4;16:894620. doi: 10.3389/fnins.2022.894620. eCollection 2022.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, affecting nearly 7-10 million people worldwide. Over the last decade, there has been considerable progress in our understanding of the genetic basis of PD, in the development of stem cell-based and animal models of PD, and in management of some clinical features. However, there remains little ability to change the trajectory of PD and limited knowledge of the underlying etiology of PD. The role of genetics versus environment and the underlying physiology that determines the trajectory of the disease are still debated. Moreover, even though protein aggregates such as Lewy bodies and Lewy neurites may provide diagnostic value, their physiological role remains to be fully elucidated. Finally, limitations to the model systems for probing the genetics, etiology and biology of Parkinson's disease have historically been a challenge. Here, we review highlights of the genetics of PD, advances in understanding molecular pathways and physiology, especially transcriptional factor (TF) regulators, and the development of model systems to probe etiology and potential therapeutic applications.
帕金森病（PD）是最常见的神经退行性疾病之一，全球近700-1000万人受其影响。在过去十年中，我们对PD的遗传基础、基于干细胞的PD模型和动物模型的开发以及一些临床特征的管理方面取得了相当大的进展。然而，改变PD病程的能力仍然有限，对PD潜在病因的了解也很有限。遗传因素与环境因素的作用以及决定疾病病程的潜在生理学机制仍存在争议。此外，尽管路易小体和路易神经突等蛋白质聚集体可能具有诊断价值，但其生理作用仍有待充分阐明。最后，用于探究帕金森病遗传学、病因学和生物学的模型系统的局限性一直是一个挑战。在此，我们综述了PD遗传学的亮点、在理解分子途径和生理学方面的进展，特别是转录因子（TF）调节剂，以及用于探究病因和潜在治疗应用的模型系统的开发。
