Advisory Committee Chair
John Crow
Advisory Committee Members
Shannon Bailey
Alvaro Estevez
Jack Lancaster
Edward Postlethwait
Document Type
Dissertation
Date of Award
2008
Degree Name by School
Doctor of Philosophy (PhD) School of Public Health
Abstract
Mutations to copper,zinc superoxide dismutase (Cu,Zn SOD or SOD1) are the only known causes of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized primarily by death of spinal motor neurons. While the molecular mechanisms responsible for motor neuron death in this disease remain to be elucidated, recent studies implicate mitochondrial dysfunction as a key factor in the pathogenesis of ALS. In support of this, we observed ALS-dependent alterations in key functions including creatine kinase activity and ATP levels, which could be linked to changes in the mitochondrial proteome. Importantly, extensive research efforts have failed to develop a treatment that significantly delays onset of the disease or extends lifespan in individuals afflicted with ALS. Studies presented in this dissertation demonstrate that Motexafin Gadolinium (MGd), an organometallic compound, markedly extends survival in G93A mice, a well-established, standardized mouse model of ALS used to elucidate molecular mechanisms of disease and the efficacy of proposed new therapeutic treatments for ALS. Although the molecular mechanism responsible for the neuroprotection afforded by MGd is not known, we observed significant drug-related alterations to the proteome, which we propose may play a role in extending life span through normalization of protein expresiv sion. Our results suggest that proteomics analysis using 2-D Differential In Gel Electrophoresis (2-D DIGE) in spinal cord extracts in the G93A mouse model may yield new protein targets which could help elucidate the molecular mechanisms of pathogenesis and protection and thereby aid selecting new therapeutic compounds.
Recommended Citation
Jones, Page, "Enzymatic And Proteomic Analysis Of Spinal Cord In A G93A Als Mouse Model" (2008). All ETDs from UAB. 3726.
https://digitalcommons.library.uab.edu/etd-collection/3726