Huang Yue, Wei Jun, Cooper Antony, Morris Margaret J
China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Genes Dis. 2022 Feb 5;10(3):786-798. doi: 10.1016/j.gendis.2021.12.015. eCollection 2023 May.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder in the elderly. As the pathogenesis of PD is still not fully understood, medications with the capacity of halting the disease progression are currently unavailable. The discovery of genes that are causative for, or increase susceptibility to PD is pivotal for the development of novel therapeutic approaches, as they are critical for the onset of PD and the molecular pathways underlying its pathogenesis. By reviewing relevant data, we discuss causative genes, and those associated with PD susceptibility and quantitative traits. Through Gene Ontology database and STRING analysis, we emphasize the roles of inorganic cation transmembrane transport pathways and hypothalamic pituitary thyroid axis, in addition to the established roles of inflammation/oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. It is hoped these insights 1) untangle the clinical complex presentations of PD, 2) reveal the interwoven molecular network leading to PD, and 3) identify critical molecular targets to facilitate novel PD drug discovery, with a view to providing improved consultation and personalized medicine for patients with PD in the future.
帕金森病（PD）是老年人中最常见的神经退行性运动障碍。由于PD的发病机制仍未完全明确，目前尚无能够阻止疾病进展的药物。发现导致PD或增加其易感性的基因对于开发新的治疗方法至关重要，因为它们对PD的发病以及其发病机制背后的分子途径至关重要。通过回顾相关数据，我们讨论了致病基因以及与PD易感性和数量性状相关的基因。通过基因本体数据库和STRING分析，我们强调了无机阳离子跨膜运输途径和下丘脑 - 垂体 - 甲状腺轴的作用，此外还强调了炎症/氧化应激和线粒体功能障碍在PD发病机制中已确立的作用。希望这些见解能够：1）理清PD复杂的临床症状；2）揭示导致PD的相互交织的分子网络；3）识别关键分子靶点以促进新型PD药物的发现，以期在未来为PD患者提供更好的咨询和个性化医疗。
