Ahmad Mir Hilal, Rizvi Moshahid Alam, Ali Mansoor, Mondal Amal Chandra
Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India; Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.
Ageing Res Rev. 2023 Mar;85:101840. doi: 10.1016/j.arr.2022.101840. Epub 2023 Jan 2.
Parkinson's disease (PD) is characterized mainly by motor dysfunctions due to the progressive loss of dopaminergic neurons. However, PD patients experience a multitude of debilitating non-motor symptoms, including depression, which may have deleteriously detrimental effects on life. Depression is multifactorial and exhibits a bimodal progression in PD, but its underlying molecular mechanisms are poorly understood. Studies demonstrating the pathophysiology of depression in PD and the specific treatment strategies for depression-like symptoms in PD patients are largely lacking, often underrated, under-recognized and, consequently, inadequately/under-treated. Nevertheless, reports suggest that the incidence of depression is approximately 20-30% of PD patients and may precede the onset of motor symptoms. Diagnosing depression in PD becomes difficult due to the clinical overlap in symptomatology between the two diseases, and the nigrostriatal dysfunction alone is insufficient to explain depressive symptoms in PD. Therefore, the current study provides an overview of the molecular mechanisms underlying the development of depression in PD and new insights into developing current antidepressant strategies to treat depression in PD. This review will identify and understand the molecular pathological mechanisms of depression in PD that will fundamentally help tailoring therapeutic interventions for depressive symptoms in PD.
帕金森病(PD)主要特征为由于多巴胺能神经元的进行性丧失导致的运动功能障碍。然而,PD患者会经历多种使人衰弱的非运动症状,包括抑郁症,这可能对生活产生有害的不利影响。抑郁症是多因素的,在PD中呈现双峰进展,但其潜在的分子机制尚不清楚。很大程度上缺乏关于PD中抑郁症病理生理学以及PD患者中类似抑郁症状的具体治疗策略的研究,这些研究常常被低估、未得到充分认识,因此治疗不足。尽管如此,报告表明抑郁症的发病率约为PD患者的20 - 30%,且可能先于运动症状出现。由于两种疾病在症状学上存在临床重叠,在PD中诊断抑郁症变得困难,而且仅黑质纹状体功能障碍不足以解释PD中的抑郁症状。因此,本研究概述了PD中抑郁症发生的分子机制,并为开发当前治疗PD中抑郁症的抗抑郁策略提供了新见解。本综述将识别并理解PD中抑郁症的分子病理机制,这将从根本上有助于为PD中的抑郁症状量身定制治疗干预措施。