亨廷顿舞蹈症诱发的心脏疾病影响多种细胞通路。

Huntington's Disease-Induced Cardiac Disorders Affect Multiple Cellular Pathways.

作者信息

Melkani Girish C

机构信息

Department of Biology, Molecular Biology and Heart Institutes, San Diego State University, San Diego, CA 92182, USA.

出版信息

React Oxyg Species (Apex). 2016 Sep;2(5):325-338. doi: 10.20455/ros.2016.859.

Abstract

Huntington's disease (HD) is a rare, inherited, progressive, and fatal neurological disorder resulting from expanded polyglutamine repeats in the huntingtin protein. While HD is predominately characterized as a disease of the central nervous system, mortality surveys and epidemiological studies reveal heart disease as one of the leading causes of death in HD patients. Emerging evidence supports a link between HD and cardiovascular disease, such as cardiac amyloidosis (accumulation of aggregates in the heart). Experimental animal and clinical studies have attempted to explain the mechanisms of HD-induced cardiac pathology in the association of protein misfolding, autophagic defects, oxidative stress, mitochondrial dysfunction, and cell death. HD is increasingly understood as a complex disease with peripheral components of cardiac and skeletal muscle pathophysiology. While the discovery of these linkages and apparent pathological markers is promising, the mechanism of HD-induced cardiac pathology and the nature of its cell autonomy remain elusive. Further study of the wide-ranging cardiac function in HD patients is needed. This review highlights published literature on the pathological factors associated with HD-induced cardiac amyloidosis and other cardiovascular diseases, and addresses gaps in this expanding area of study. Through comprehensive experimental and clinical studies, potential drugs can be tested to attenuate and/or ameliorate HD-induced cardiac pathology and mortality.

摘要

亨廷顿舞蹈症(HD)是一种罕见的、遗传性的、进行性的致命性神经疾病,由亨廷顿蛋白中多聚谷氨酰胺重复序列扩增所致。虽然HD主要被认为是一种中枢神经系统疾病,但死亡率调查和流行病学研究显示,心脏病是HD患者的主要死因之一。新出现的证据支持HD与心血管疾病之间存在联系,如心脏淀粉样变性(心脏中聚集体的积累)。实验动物和临床研究试图解释在蛋白质错误折叠、自噬缺陷、氧化应激、线粒体功能障碍和细胞死亡的关联中,HD诱发心脏病理的机制。HD越来越被认为是一种具有心脏和骨骼肌病理生理学外周成分的复杂疾病。虽然这些联系和明显的病理标志物的发现很有前景,但HD诱发心脏病理的机制及其细胞自主性的本质仍不清楚。需要对HD患者广泛的心脏功能进行进一步研究。本综述重点介绍了已发表的关于与HD诱发的心脏淀粉样变性和其他心血管疾病相关的病理因素的文献,并阐述了这一不断扩展的研究领域中的空白。通过全面的实验和临床研究,可以测试潜在药物以减轻和/或改善HD诱发的心脏病理和死亡率。

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