Differential Proteomic Investigations Of Normal Appearing Gray Matter In Multiple Sclerosis And Control Post-Mortem Brain Tissue.

Mitochondrial dysfunction has been proposed to play a role in the neuropathology of multiple sclerosis (MS). To more thoroughly and efficiently elucidate potential alterations in the expression of mitochondrial and related proteins, The mitochondrial proteome in motor and parietal cortex has been characterized using Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS). Principal component analysis (PCA) and hierarchical clustering techniques were used to analyze the differential patterns of SELDI-TOF spectra to reveal clusters of peaks which distinguished MS from control samples. Nine proteins were found to be responsible for distinguishing disease from control. Peptide fingerprint mapping and liquid chromatography tandem mass spectrometry unambiguously identified these differentially expressed proteins. Five proteins identified are involved in respiration including cytochrome c oxidase (COX) subunits 5a, 5b and 6c, the brain specific isozyme of creatine kinase, and hemoglobin ß-chain. A sixth differentially expressed protein identified was myelin basic protein (MBP), a major component of myelin. Lastly, glial fibrillary acidic protein was found to be differentially expressed. This study provided evidence of key differentially expressed proteins and peptides which play a critical role in the early molecular events in MS pathology and may lead to the development of superior therapeutics agents and possible cures for this disorder.

Name thesis:degree_name

PHD

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

College of Arts and Sciences / Department of Chemistry

Grantor dc:publisher

Kent State University

Year dc:date

2013

Author dc:creator

• Broadwater, Laurie A.

Contributors dc:contributor

• Gregory, Roger
• McDonough, Jennifer

• Biochemistry
• Neurosciences

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=kent1366063427

OAI identifier oai:identifier

oai:etd.ohiolink.edu:kent1366063427