Proteasome dysfunction in aged human α-synuclein transgenic mice
Proteasome dysfunction in aged human α-synuclein transgenic mice
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DOI：
10.1016/j.nbd.2006.02.004
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发表时间：
2006-07-01
影响因子：
6.1
通讯作者：
Richfield, Eric K.
中科院分区：
文献类型：
--
作者：
Chen, Li;Thiruchelvam, Mona J.;Richfield, Eric K.
据推测，帕金森氏病可能存在蛋白酶体功能缺陷。我们研究了转基因和非转基因小鼠脑内三个区域的泛素-蛋白酶体系统。与非转基因小鼠相比，表达双突变形式的人α-突触核蛋白的小鼠有明显的损伤，而表达野生型基因的小鼠的变化较小。Hm(2)α-SYN-39的显著异常包括205介导的蛋白分解活性、19S蛋白酶体亚基Rpt1和Rpn2的水平以及可溶性总高相对分子质量泛素交叉反应蛋白的水平。品系HWα-SYN-5有明显但限制性的蛋白酶体异常。损伤的严重程度与先前发现的黑质多巴胺能神经元丢失成正比。Rpn2水平与Rpt1水平、20S蛋白酶体活性、可溶性高相对分子质量泛素交叉反应蛋白水平显著相关。症状系Hm(2)α-SYN-39小鼠的这些异常与帕金森氏病患者组织中发现的异常一致。(C)2006 Elsevier Inc.保留所有权利。
A deficit in proteasome function in Parkinson's disease has been speculated. We characterized the ubiquitin-proteasome system in three regions of brain from transgenic and nontransgenic littermates. Mice expressing a doubly mutated form of human alpha-synuclein had significant impairments whereas mice expressing the wild-type gene had lesser changes compared to nontransgenic littermates. Significant abnormalities in line hm(2)alpha-SYN-39 included declines in 205-mediated proteolytic activity, the level of the 19S proteasome subunits Rpt1 and Rpn2, and the level of soluble total high MW ubiquitin cross-reacting proteins. Line hw alpha-SYN-5 had significant, but restricted proteasome abnormalities. The severity of impairment was proportional to the substantia nigra dopaminergic neuronal loss previously identified. There were significant correlations between the level of Rpn2 with the level of Rpt1, the activity of the 20S proteasome, and the level of soluble high MW ubiquitin cross-reacting proteins. These abnormalities in symptomatic line hm(2)alpha-SYN-39 mice are consistent with abnormalities identified in tissue from patients with Parkinson's disease. (c) 2006 Elsevier Inc. All rights reserved.