Our aged population is poised to expand dramatically within the next
decade. In Alzheimers disease (AD) pathogenesis studies, the end point
hallmarks or lesions are known and well studied; however, the exact processes
leading to these lesions are not. Defining early pathological events at the
molecular and protein level and targeting appropriate therapies to pre-clinical or
early stage dementia is necessary to avert the coming public health crisis. This
project showed that lipid peroxidation products can lead to microtubule
dysfunction that is characteristic of AD and that this is associated with their
accumulation on tau from among the cytoskeletal proteins investigated. In
contrast, another type of protein oxidation was observed selectively on Beta-III
tubulin using mass spectrometry. Together, these data indicate that multiple
oxidative modifications to cytoskeletal proteins are likely occurring in AD and that
these can contribute to cytoskeletal dysfunction, leading to a modified model of
AD pathogenesis. Furthermore, the results suggest that approaches to limit protein oxidation may have the downstream effect of suppressing protein
insolubility and its consequences. Perhaps, with further investigation, studies will
be able to define drug-treatable targets to prevent and slow neurodegenerative
disease progression.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11182005-151111 |
| Date | 05 December 2005 |
| Creators | Boutte, Angela Monique |
| Contributors | John Oates, William Valentine, Olivier Boutaud, Michael McDonald, Thomas J. Montine, Elaine Sanders-Bush |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11182005-151111/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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