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α-突触核蛋白阻断内质网-高尔基体运输，而Rab1可挽救帕金森病模型中的神经元损失。

Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models.

作者信息

Cooper Antony A, Gitler Aaron D, Cashikar Anil, Haynes Cole M, Hill Kathryn J, Bhullar Bhupinder, Liu Kangning, Xu Kexiang, Strathearn Katherine E, Liu Fang, Cao Songsong, Caldwell Kim A, Caldwell Guy A, Marsischky Gerald, Kolodner Richard D, Labaer Joshua, Rochet Jean-Christophe, Bonini Nancy M, Lindquist Susan

机构信息

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.

出版信息

Science. 2006 Jul 21;313(5785):324-8. doi: 10.1126/science.1129462. Epub 2006 Jun 22.

DOI:10.1126/science.1129462
PMID:16794039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1983366/
Abstract

Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following alphaSyn expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

摘要

α-突触核蛋白（αSyn）错误折叠与包括帕金森病（PD）在内的几种毁灭性神经退行性疾病相关。在酵母细胞和神经元中，αSyn积累具有细胞毒性，但其正常功能或病理生物学知之甚少。酵母中αSyn表达后最早出现的缺陷是内质网（ER）到高尔基体的囊泡运输受阻。在全基因组筛选中，最大一类毒性调节因子是在同一步骤发挥作用的蛋白质，包括与细胞质αSyn包涵体相关的Rab鸟苷三磷酸酶Ypt1p。Rab1（哺乳动物YPT1的同源物）的表达升高可保护PD动物模型免受αSyn诱导的多巴胺能神经元损失。因此，突触核蛋白病可能是由于与特定神经元独特生物学相互作用的基本细胞功能中断，使其特别易受影响所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/d9dc92694162/nihms15898f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/9c88be6a88e6/nihms15898f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/751be8bbf867/nihms15898f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/e505f01c0af0/nihms15898f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/f87ba69b214e/nihms15898f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/d9dc92694162/nihms15898f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/9c88be6a88e6/nihms15898f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/751be8bbf867/nihms15898f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/e505f01c0af0/nihms15898f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/f87ba69b214e/nihms15898f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2352/1983366/d9dc92694162/nihms15898f5.jpg

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