Guo Mengyuan, Ji Xunming, Liu Jia
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Aging Neurosci. 2022 Jul 26;14:919343. doi: 10.3389/fnagi.2022.919343. eCollection 2022.
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, with typical motor symptoms as the main clinical manifestations. At present, there are about 10 million patients with PD in the world, and its comorbidities and complications are numerous and incurable. Therefore, it is particularly important to explore the pathogenesis of PD and find possible therapeutic targets. Because the etiology of PD is complex, involving genes, environment, and aging, finding common factors is the key to identifying intervention targets. Hypoxia is ubiquitous in the natural environment and disease states, and it is considered to be closely related to the etiology of PD. Despite research showing that hypoxia increases the expression and aggregation of alpha-synuclein (α-syn), the most important pathogenic protein, there is still a lack of systematic studies on the role of hypoxia in α-syn pathology and PD pathogenesis. Considering that hypoxia is inextricably linked with various causes of PD, hypoxia may be a co-participant in many aspects of the PD pathologic process. In this review, we describe the risk factors for PD, and we discuss the possible role of hypoxia in inducing PD pathology by these risk factors. Furthermore, we attribute the pathological changes caused by PD etiology to oxygen uptake disorder and oxygen utilization disorder, thus emphasizing the possibility of hypoxia as a critical link in initiating or promoting α-syn pathology and PD pathogenesis. Our study provides novel insight for exploring the pathogenesis and therapeutic targets of PD.
帕金森病（PD）是仅次于阿尔茨海默病的第二常见神经退行性疾病，以典型运动症状为主要临床表现。目前，全球约有1000万帕金森病患者，其合并症和并发症众多且难以治愈。因此，探索帕金森病的发病机制并寻找可能的治疗靶点尤为重要。由于帕金森病的病因复杂，涉及基因、环境和衰老等因素，找到共同因素是确定干预靶点的关键。缺氧在自然环境和疾病状态中普遍存在，被认为与帕金森病的病因密切相关。尽管研究表明缺氧会增加最重要的致病蛋白α-突触核蛋白（α-syn）的表达和聚集，但关于缺氧在α-syn病理学和帕金森病发病机制中的作用仍缺乏系统研究。鉴于缺氧与帕金森病的各种病因密切相关，缺氧可能在帕金森病病理过程的多个方面共同起作用。在本综述中，我们描述了帕金森病的危险因素，并讨论了缺氧通过这些危险因素诱导帕金森病病理的可能作用。此外，我们将帕金森病病因引起的病理变化归因于氧摄取障碍和氧利用障碍，从而强调缺氧作为启动或促进α-syn病理学和帕金森病发病机制关键环节的可能性。我们的研究为探索帕金森病的发病机制和治疗靶点提供了新的见解。
