Smith R, Brundin P, Li J-Y
Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 221 84, Lund, Sweden.
Cell Mol Life Sci. 2005 Sep;62(17):1901-12. doi: 10.1007/s00018-005-5084-5.
Huntington's disease (HD) is caused by a polyglutamine expansion in the protein huntingtin and is characterized by intraneuronal inclusions and widespread neuronal death at the late stage of the disease. In research, most of the emphasis has been on understanding the cell death and its mechanisms. Until recently, it was believed that the vast majority, if not all, of the symptoms in HD are a direct consequence of neurodegeneration. However, increasing evidence shows that subtle alterations in synaptic function could underlie the early symptoms. It is of particular interest to understand the nature of this neuronal dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This review describes recent advances in understanding synaptic dysfunction in HD.
亨廷顿舞蹈症（HD）由亨廷顿蛋白中的多聚谷氨酰胺扩增引起，其特征是在疾病晚期出现神经元内包涵体和广泛的神经元死亡。在研究中，大部分重点都放在了理解细胞死亡及其机制上。直到最近，人们还认为，HD中绝大多数（如果不是全部）症状都是神经退行性变的直接后果。然而，越来越多的证据表明，突触功能的细微改变可能是早期症状的基础。了解这种神经元功能障碍的本质特别令人感兴趣。正常的亨廷顿蛋白与各种细胞骨架和突触小泡蛋白相互作用，这些蛋白对于胞吐作用和胞吞作用至关重要。突变的亨廷顿蛋白与其相关伙伴之间相互作用的改变可能导致HD中异常的突触传递。本综述描述了在理解HD突触功能障碍方面的最新进展。
