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TRICHOSTATIN A AND DIHYDROTESTOSTERONE AS POTENTIAL
MULTI-SYSTEMIC DRUGS FOR AMYOTROPHIC LATERAL SCLEROSIS
by
Young-Eun Yoo
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
May 2010
Copyright 2010 Young-Eun Yoo
Object Description
| Title | Trichostatin A and dihydrotestosterone as potential multi-systemic drugs for amyotrophic lateral sclerosis |
| Author | Yoo, Young-Eun |
| Author email | youngeuy@usc.edu; youngeuy@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2009-12-11 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-02-02 |
| Advisor (committee chair) | Ko, Chien-Ping |
| Advisor (committee member) |
Butler, Samantha J. Pike, Christian J. Youn, Jang H. |
| Abstract | Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) is a lethal neurodegenerative disease characterized by motor neuron loss, progressive muscle weakness, atrophy and paralysis. ALS is the most common motoneuron disease in human adults, and currently, there is no cure for ALS. Although ALS is a motoneuron disease, non-neuronal cells have been implicated in modulating motoneuron degeneration and disease progression. Because trichostatin A (TSA) and dihydrotestosterone (DHT) have shown beneficial effects on multiple cell types implicated in ALS, we examined their effects as a potential drug in a mouse model of ALS, SOD1 G93A mice.; The treatment of TSA or DHT to early symptomatic SOD1 G93A mice ameliorated muscle atrophy, NMJ denervation, axonal degeneration, and motoneuron death, which are the pathological characteristics found in SOD1 G93A mice. The improved morphology in TSA- or DHT-treated SOD1 G93A mice was accompanied by improved motor functions as well as prolonged lifespan. The beneficial effect exerted by TSA or DHT might be mediated by their potential effects on multiple cell types implicated in ALS. Since ALS is a disease that involves neuronal and non-neuronal cell types, TSA or DHT treatment, which can target multiple cell types, might be an effective strategy to slow motoneuron loss, as well as to improve motor performance that may lead to the improved quality of life for ALS patients. |
| Keyword | amyotrophic lateral sclerosis; SOD1 G93A; transgenic mice; motor neurons; motor behavior; therapy |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2827 |
| Rights | Yoo, Young-Eun |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Yoo-3420 |
| Archival file | uscthesesreloadpub_Volume56/etd-Yoo-3420.pdf |
Description
| Title | Page 1 |
| Full text | TRICHOSTATIN A AND DIHYDROTESTOSTERONE AS POTENTIAL MULTI-SYSTEMIC DRUGS FOR AMYOTROPHIC LATERAL SCLEROSIS by Young-Eun Yoo A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) May 2010 Copyright 2010 Young-Eun Yoo |
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