Date of Graduation

2002

Document Type

Thesis

Degree Type

MS

Committee Chair

Michael R. Gunther

Abstract

The pathogenesis of familial amyotrophic lateral sclerosis (fALS), a fatal neurodegenerative disease that sometimes results from SOD1 mutations, may involve the peroxidase reaction of the SOD1 protein. The aim of this thesis was to test the hypothesis that the peroxidase reaction of SOD results in SOD-centered peroxyl radical formation. The source of oxygen incorporated into 2-oxohistidine was to have been determined using HPLC/Mass spectrometry. This aim was not accomplished. UV-Visible difference spectrometry provided evidence for a peroxyl radical in this reaction. 2-oxohistidine formation was shown to be oxygen dependent and inhibited by the spin-trap MNP (Gunther, Peters, and Sivaneri 2002 JBC). The generation of free radicals is important in ALS, since free radical production results in cellular damage. The putative SOD peroxyl radical could contribute to oxidative cellular damage. Prevention of free radical generation might provide avenues for the treatment of ALS resulting from mutations with the SOD1 gene.

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