Tiwari Shubhangini, Singh Sarika
Department of Neurosciences and Ageing Biology and Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Neuroscientist. 2021 Aug;27(4):340-354. doi: 10.1177/1073858420942211. Epub 2020 Jul 25.
Parkinson's disease (PD) pathology involves degeneration of nigrostriatal pathway, postulating symptoms associated with age, environment, and genetic anomalies, including nonlinear disease progression. Hallmark characteristics of PD include dopaminergic neuronal degeneration and death, which may also be exhibited by other neurological diseases, making the diagnosis of the disease intricate at early stage. Such obscure diagnosis of the disease, limited symptomatic improvements with available therapeutics, and their inability to modify the disease status instigate us to appraise the past research and formulate the colligating comprehensive insights. This review is accentuating on the role of nitric oxide, endoplasmic reticulum stress, and their association with the ubiquitin proteasome system (UPS) during PD pathology involving focus on ubiquitin ligases due to their regulatory functions. Meticulous understanding of these major disease-related pathological events and their functional alliance may render novel dimensions for better understanding of disease etiology, related mechanisms, as well as direction toward witnessing of new therapeutic targets for the management of Parkinson's patients.
帕金森病(PD)的病理过程涉及黑质纹状体通路的退化,其发病与年龄、环境和基因异常有关,包括疾病的非线性进展。PD的标志性特征包括多巴胺能神经元的退化和死亡,其他神经疾病也可能出现这些症状,这使得该疾病在早期阶段的诊断变得复杂。这种疾病诊断的模糊性、现有治疗方法有限的症状改善效果以及它们无法改变疾病状态,促使我们评估过去的研究并形成综合全面的见解。本综述着重探讨一氧化氮、内质网应激的作用,以及它们在PD病理过程中与泛素蛋白酶体系统(UPS)的关联,由于泛素连接酶具有调节功能,因此重点关注泛素连接酶。对这些与疾病相关的主要病理事件及其功能联系的深入理解,可能为更好地理解疾病病因、相关机制以及寻找帕金森病患者管理的新治疗靶点提供新的思路。