Journal
NEUROSCIENCE
Volume 132, Issue 2, Pages 313-324Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2004.12.022
Keywords
Alzheimer's disease; amyloid beta-peptide (1-42); proteomics; oxidative stress; neurodegeneration
Categories
Funding
- NIA NIH HHS [AG-05119, AG-10836] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [P01AG010836] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Protein oxidation has been shown to result in loss of protein function. There is increasing evidence that protein oxidation plays a role in the pathogenesis of Alzheimer's disease (AD). Amyloid beta-peptide (1-42) [A beta(1-42)] has been implicated as a mediator of oxidative stress in AD. Additionally, A beta(1-42) has been shown to induce cholinergic dysfunction when injected into rat brain, a finding consistent with cholinergic deficits documented in AD. In this study, we used proteomic techniques to examine the regional in vivo protein oxidation induced by A beta(1-42) injected into the nucleus basalis magnocellularis (NBM) of rat brain compared with saline-injected control at 7 days post-injection. In the cortex, we identified glutamine synthetase and tubulin beta chain 15/alpha, while, in the NBM, we identified 14-3-3 zeta and chaperonin 60 (HSP60) as significantly oxidized. Extensive oxidation was detected in the hippocampus where we identified 14-3-3 zeta, beta-synuclein, pyruvate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase 1. The results of this study suggest that a single injection of A beta(1-42) into NBM can have profound effects elsewhere in the brain. The results further suggest that A beta(1-42)-induced oxidative stress in rat brain mirrors some of those proteins oxidized in AD brain and leads to oxidized proteins, which when inserted into their respective biochemical pathways yields insight into brain dysfunction that can lead to neurodegeneration in AD. (c) 2005 IBRO. Published by Elsevier Ltd. 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