Faculté de Médecine, département de Psychiatrie et Neurosciences, Université Laval, Québec, QC, Canada Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, QC, Canada.
Faculté de Médecine, département de Psychiatrie et Neurosciences, Université Laval, Québec, QC, Canada Centre de Recherche du CHU de Québec, Axe Neurosciences, Québec, QC, Canada
Brain. 2016 Apr;139(Pt 4):1014-25. doi: 10.1093/brain/aww021. Epub 2016 Mar 11.
Tauopathies are a subclass of neurodegenerative diseases typified by the deposition of abnormal microtubule-associated tau protein within the cerebral tissue. Alzheimer's disease, progressive supranuclear palsy, chronic traumatic encephalopathy and some fronto-temporal dementias are examples of the extended family of tauopathies. In the last decades, intermittent reports of cerebral tau pathology in individuals afflicted with Huntington's disease-an autosomal dominant neurodegenerative disorder that manifests by severe motor, cognitive and psychiatric problems in adulthood-have also begun to surface. These observations remained anecdotal until recently when a series of publications brought forward compelling evidence that this monogenic disorder may, too, be a tauopathy. Collectively, these studies reported that: (i) patients with Huntington's disease present aggregated tau inclusions within various structures of the brain; (ii) tau haplotype influences the cognitive function of Huntington's disease patients; and (iii) that the genetic product of the disease, the mutant huntingtin protein, could alter tau splicing, phosphorylation, oligomerization and subcellular localization. Here, we review the past and current evidence in favour of the postulate that Huntington's disease is a new member of the family of tauopathies.
tau 病是神经退行性疾病的一个子类,其特征是脑组织内异常微管相关 tau 蛋白的沉积。阿尔茨海默病、进行性核上性麻痹、慢性创伤性脑病和一些额颞叶痴呆症是 tau 病大家族的例子。在过去的几十年里,人们开始间歇性地报告亨廷顿病患者的大脑 tau 病理学,亨廷顿病是一种常染色体显性神经退行性疾病,在成年期表现为严重的运动、认知和精神问题。直到最近,一系列出版物提出了令人信服的证据,表明这种单基因疾病也可能是一种 tau 病,这些观察结果才变得有据可依。这些研究共同表明:(i)亨廷顿病患者的大脑各结构中存在聚集的 tau 包涵体;(ii)tau 单倍型影响亨廷顿病患者的认知功能;(iii)该疾病的遗传产物,突变亨廷顿蛋白,可改变 tau 的剪接、磷酸化、寡聚化和亚细胞定位。在这里,我们回顾了过去和现在的证据,支持亨廷顿病是 tau 病家族的新成员这一假设。