Patel Dishank, Soni Ritu, Shah Jigna
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382481, India.
ACS Chem Neurosci. 2024 Sep 27. doi: 10.1021/acschemneuro.4c00507.
Parkinson's disease (PD) is the second most prevailing degenerative disease that deals with dopaminergic neuronal loss and deficiency of dopamine in SNpc and striatum. Manifestations primarily include motor symptoms like tremor, rigidity, and akinesia/dyskinesia along with some nonmotor symptoms like GI and olfactory dysfunction. α-Synuclein pathogenesis is the major cause behind progression of PD; however there are many underlying molecular mechanisms behind the pathophysiology of PD. Sirtuins are small molecular deacetylases that have an imperative role in pathology of such neurodegenerative disorders like PD. Sirtuins are majorly classified according to their location; nuclear (SIRT1,7,6), mitochondrial sirtuins (SIRT3-5), and cytosolic (SIRT2). These actively take part in pathological development and possess independent actions. In this review, the role of nuclear sirtuins is individualistically explored for better understanding of PD pathology and development of advanced therapeutics targeting sirtuins.
帕金森病（PD）是第二常见的退行性疾病，涉及黑质致密部（SNpc）和纹状体中多巴胺能神经元的丧失以及多巴胺的缺乏。其表现主要包括运动症状，如震颤、僵硬和运动不能/运动障碍，以及一些非运动症状，如胃肠道和嗅觉功能障碍。α-突触核蛋白发病机制是PD进展的主要原因；然而，PD病理生理学背后还有许多潜在的分子机制。沉默调节蛋白是小分子脱乙酰酶，在PD等神经退行性疾病的病理过程中起着至关重要的作用。沉默调节蛋白主要根据其位置进行分类；细胞核型（SIRT1、7、6）、线粒体型沉默调节蛋白（SIRT3 - 5）和胞质型（SIRT2）。它们积极参与病理发展并具有独立作用。在本综述中，将单独探讨细胞核型沉默调节蛋白的作用，以更好地理解PD病理以及开发针对沉默调节蛋白的先进治疗方法。
