Goryunov Dmitry, Liem Ronald K H
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
J Clin Invest. 2007 Mar;117(3):590-2. doi: 10.1172/JCI31505.
Protein accumulation is a hallmark of many neurodegenerative disorders. In Alzheimer's disease (AD), a hyperphosphorylated form of the protein tau (p-tau) forms intracellular inclusions known as neurofibrillary tangles. Deposits of p-tau have also been found in the brains of patients with Down's syndrome, supranuclear palsy, and prion disease. Mutations in tau have been causally associated with at least one inherited neurologic disorder, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), implying that tau abnormalities by themselves can be a primary cause of degenerative diseases of the CNS. Removal of these p-tau species may occur by both chaperone-mediated refolding and degradation. In this issue of the JCI, Dickey and colleagues show that a cochaperone protein, carboxyl terminus of Hsp70-interacting protein (CHIP), in a complex with Hsp90 plays an important role in the removal of p-tau (see the related article beginning on page 648). Pharmacologic manipulation of Hsp90 may be used to alleviate p-tau accumulation in disease.
蛋白质积累是许多神经退行性疾病的一个标志。在阿尔茨海默病（AD）中，蛋白质tau的一种高度磷酸化形式（p-tau）形成细胞内包涵体，即神经原纤维缠结。在唐氏综合征、核上性麻痹和朊病毒病患者的大脑中也发现了p-tau沉积物。tau基因突变与至少一种遗传性神经疾病——与17号染色体相关的额颞叶痴呆伴帕金森综合征（FTDP-17）有因果关系，这意味着tau异常本身可能是中枢神经系统退行性疾病的主要原因。这些p-tau蛋白的清除可能通过伴侣蛋白介导的重折叠和降解两种方式进行。在本期《临床研究杂志》中，迪基及其同事表明，一种辅助伴侣蛋白——Hsp70相互作用蛋白的羧基末端（CHIP），与Hsp90形成复合物，在清除p-tau蛋白方面发挥着重要作用（见第648页开始的相关文章）。对Hsp90进行药物操控可能用于减轻疾病中p-tau蛋白的积累。
