Potassium channel dysfunction in neurons and astrocytes in Huntington’s disease.
Potassium channel dysfunction in neurons and astrocytes in Huntington’s disease.
复制标题
亨廷顿病中神经元和星形胶质细胞的钾通道功能障碍。
DOI：
10.1111/cns.12804
复制
发表时间：
2018
影响因子：
5.5
通讯作者：
Tong XP
中科院分区：
文献类型：
--
作者：
Zhang X;Wan JQ;Tong XP
亨廷顿病（HD）是一种迟发性致死性神经退行性疾病，以进行性运动障碍、精神症状和认知障碍为特征。编码存在于蛋白亨廷顿（Htt）中的谷氨酰胺的胞嘧啶-腺嘌呤-鸟嘌呤（CAG）三联体扩增产生广泛的神经元和神经胶质病理学。突变的亨廷顿蛋白（mHtt）核聚集体是皮质和纹状体神经元变性、神经元炎症、细胞凋亡和最终细胞损失的主要原因。HD神经退行性变发病机制的确切机制仍然知之甚少，HD患者目前没有治愈方法。钾离子通道在大多数细胞类型中广泛表达。在神经元中，它们在设定静息膜电位、介导动作电位的快速复极化阶段和控制膜电位的阈下振荡中起关键作用。在神经胶质细胞中，它们的主要贡献是维持静息膜电位和缓冲细胞外K+。因此，钾通道在生理和病理脑状况中都具有重要功能。本文就近年来利用不同的HD小鼠模型研究HD病理过程中钾通道的研究进展作一综述。探索大脑中钾通道的功能障碍说明了靶向该通道治疗HD的新方法。
Huntington's disease (HD) is a late‐onset fatal neurodegenerative disease, characterized by progressive movement disorders, psychiatric symptoms, and cognitive impairment. The cytosine‐adenine‐guanine (CAG) triplet expansion encoding glutamine present in the protein huntingtin (Htt), produces widespread neuronal and glial pathology. Mutant huntingtin (mHtt) nuclear aggregates are the primary cause of cortical and striatal neuron degeneration, neuronal inflammation, apoptosis and eventual cell loss. The precise mechanisms underlying the pathogenesis of neurodegeneration in HD remain poorly understood and HD patients have no current cure. Potassium channels are widely expressed in most cell types. In neurons, they play a crucial role in setting the resting membrane potential, mediating the rapid repolarization phase of the action potential and controlling sub‐threshold oscillations of membrane potentials. In glial cells, their major contributions are maintaining the resting membrane potential and buffering extracellular K+. Thus, potassium channels have an essential function in both physiological and pathological brain conditions. This review summarizes recent progress on potassium channels involved in the pathology of HD by using different HD mouse models. Exploring the dysfunction of potassium channels in the brain illustrates new approaches for targeting this channel for the treatment of HD.