The effects of Parkinson's disease mimetics on the proteasomal and neurofilament systems in SH-SY5Y cells

CANEDA-FERRÓN, B., 2006. The effects of Parkinson's disease mimetics on the proteasomal and neurofilament systems in SH-SY5Y cells. PhD, Nottingham Trent University.

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Abstract

Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson's disease, linked recently to proteasomal dysfunction. This study analyses how these factors influence the various activities of the proteasome in SH-SY5Y human neuroblastoma cells treated with the PD mimetics MPP+ (a complex I inhibitor) or dopamine. Treatment with these toxins led to dose and time dependent reductions in ATP and glutathione levels and also chymotrypsin-like and postacidic-like activities; however, trypsin-like activity was unaffected. Antioxidants blocked the effects of dopamine but not MPP+, suggesting that oxidative stress was more important in the dopamine-mediated effects. With MPP+, ATP depletion was a pre-requisite for loss of proteasomal function. This study also shows that addition of MPP+ or dopamine to purified samples of the human 20S proteasome also reduced proteasomal activities; with dopamine being most damaging. As was the case with toxin-treated cells chymotrypsin-like activity was the most sensitive and trypsin-like activity, the least sensitive. The direct effect of both compounds on proteasomal activity was, at least, partly due to oxidative damage to the proteasome, since the antioxidant vitamin C could partially alleviate the proteasomal impairment.

Item Type: Thesis
Creators: Caneda-Ferrón, B.
Date: 2006
Rights: This work is the intellectual property of the author, and may also be owned by the research sponsor(s) and/or Nottingham Trent University. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, of if a more substantial copy is required, should be directed in the first instance to the author.
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 09:34
Last Modified: 09 Oct 2015 09:34
URI: http://irep.ntu.ac.uk/id/eprint/105

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