Fitzgerald Julia C, Plun-Favreau Helene
Department of Molecular Neuroscience, Institute of Neurology, University College London, UK.
FEBS J. 2008 Dec;275(23):5758-66. doi: 10.1111/j.1742-4658.2008.06708.x.
Rare, inherited mutations causing familial forms of Parkinson's disease have provided insight into the molecular mechanisms that underlie the genetic and sporadic forms of this disease. Loss of protein function resulting from autosomal-recessive mutations in PTEN-induced putative kinase 1 (PINK1), Parkin and DJ-1 has been linked to mitochondrial dysfunction, accumulation of abnormal and misfolded proteins, impaired protein clearance and oxidative stress. Accumulating evidence suggests that wild-type PINK1, Parkin and DJ-1 may be key components of neuroprotective signalling cascades that run in parallel, interact via cross talk or converge in a common pathway.
导致帕金森病家族性形式的罕见遗传突变,为深入了解这种疾病的遗传和散发性形式所依据的分子机制提供了线索。由常染色体隐性突变引起的PTEN诱导激酶1(PINK1)、帕金蛋白(Parkin)和DJ-1蛋白功能丧失,与线粒体功能障碍、异常和错误折叠蛋白的积累、蛋白质清除受损以及氧化应激有关。越来越多的证据表明,野生型PINK1、帕金蛋白和DJ-1可能是并行运行、通过相互作用或汇聚于共同途径的神经保护信号级联反应的关键组成部分。