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G蛋白偶联受体在神经退行性疾病中的作用:治疗干预途径

The role of GPCRs in neurodegenerative diseases: avenues for therapeutic intervention.

作者信息

Huang Yunhong, Todd Nicholas, Thathiah Amantha

机构信息

Department of Neurobiology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA.

University of Pittsburgh Brain Institute, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, BST3, Pittsburgh, PA 15213, USA.

出版信息

Curr Opin Pharmacol. 2017 Feb;32:96-110. doi: 10.1016/j.coph.2017.02.001. Epub 2017 Mar 10.

Abstract

Neurodegenerative diseases represent a large group of neurological disorders with heterogeneous clinical and pathological profiles. The majority of current therapeutic strategies provide temporary symptomatic relief but do not target the underlying disease pathobiology and thus do not affect disease progression. G protein-coupled receptors (GPCRs) are among the most successful targets for therapeutic development of central nervous system (CNS) disorders. Many current clinical therapeutic agents act by targeting this class of receptors and downstream signaling pathways. Here, we review evidence that perturbation of GPCR function contributes to the pathophysiology of various neurodegenerative diseases, including Alzheimer's disease, Frontotemporal dementia, Vascular dementia, Parkinson's disease, and Huntington's disease.

摘要

神经退行性疾病是一大类具有异质性临床和病理特征的神经系统疾病。目前的大多数治疗策略只能提供暂时的症状缓解,但并未针对潜在的疾病病理生物学,因此无法影响疾病进展。G蛋白偶联受体(GPCRs)是中枢神经系统(CNS)疾病治疗开发中最成功的靶点之一。许多当前的临床治疗药物通过靶向这类受体和下游信号通路发挥作用。在此,我们综述了相关证据,即GPCR功能紊乱参与了包括阿尔茨海默病、额颞叶痴呆、血管性痴呆、帕金森病和亨廷顿病在内的各种神经退行性疾病的病理生理学过程。

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