University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France; CHU Grenoble Alpes, 38000 Grenoble, France.
University Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, 38000 Grenoble, France; INSERM, U1216, 38000 Grenoble, France.
Neuron. 2016 Mar 2;89(5):910-26. doi: 10.1016/j.neuron.2016.02.003.
Huntingtin (HTT) is now a famous protein because an abnormal expansion of a glutamine stretch (polyQ) in its N-terminal sequence leads to the devastating neurodegenerative disorder Huntington's disease (HD). The gene encoding huntingtin, HTT, and its dominantly inherited mutation were identified more than 20 years ago. Subsequently, in the hope of finding a cure for HD, there has been intense research aimed at understanding the molecular mechanisms underlying the deleterious effects of the presence of the abnormal polyQ expansion in HTT. Notwithstanding with the value of this approach, evidence has been emerging of a potential role of context and function of the HTT protein in the specificity and severity of the pathogenicity. HTT is ubiquitous both at the tissue and subcellular levels. It interacts with many partners and has long been considered having no clearly defined cellular function. Based on research over the past 20 years, specifically focused on the function of wild-type HTT, we reconsider the literature describing HTT-regulated molecular and cellular mechanisms that could be dysfunctional in HD and their possible physiological consequences for patients.
亨廷顿蛋白（HTT）现在是一种著名的蛋白质，因为其 N 端序列中谷氨酰胺延伸（多聚 Q）的异常扩展导致了毁灭性的神经退行性疾病亨廷顿病（HD）。编码亨廷顿蛋白（HTT）的基因及其显性遗传突变在 20 多年前被鉴定出来。随后，为了寻找治疗 HD 的方法，人们进行了大量的研究，旨在了解 HTT 中异常多聚 Q 扩展存在的有害影响的分子机制。尽管这种方法具有价值，但越来越多的证据表明，HTT 蛋白的上下文和功能在致病性的特异性和严重程度上可能具有潜在作用。HTT 在组织和亚细胞水平上都普遍存在。它与许多合作伙伴相互作用，长期以来一直被认为没有明确的细胞功能。基于过去 20 年的研究，特别是针对野生型 HTT 功能的研究，我们重新考虑了描述 HD 中可能功能失调的 HTT 调节的分子和细胞机制及其对患者可能产生的生理后果的文献。
