Journal
NEUROBIOLOGY OF DISEASE
Volume 23, Issue 1, Pages 120-126Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.02.004
Keywords
Parkinson's disease; ubiquitin-proteasome system; proteolytic stress; transgenic mice; dopamine system; 19S and 205 proteasome; alpha synuclein
Categories
Funding
- NCI NIH HHS [CA83875] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available