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|Title:||Expression of BEX1 and MSK1 in motor neurons with differential susceptibility to degeneration in amyotrophic lateral sclerosis in transgenic rats and human patients|
|Abstract:||Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease that is characterized by progressive weakness, muscle atrophy, and paralysis. Even though the majority of motor neurons begin to degenerate at the onset of ALS, there exist a few motor neuron populations that seemingly resist degeneration until the very late stages of the disease. Earlier studies in our laboratory employing laser capture microdissection and comparative microarrays identified two genes with differential expression between the resistant and vulnerable motor neuron populations: brain-linked X-expressed 1 (BEX1) and mitogen and stress-activated kinase 1 (MSK1); these studies also demonstrated the differential expression of BEX1 and MSK1 protein in wild-type rodents. This current study utilizes immunohistochemical techniques to confirm the differential expression of BEX1 and MSK1 in not only pre-symptomatic and symptomatic ALS transgenic rats but also in control and ALS human brain tissue. BEX1 protein expression was higher in the ALS-resistant motor neuron populations, while MSK1 protein expression was higher in the ALS-vulnerable motor neuron populations. In addition, as the disease progressed from the early to late stages, parallel decreases in levels of BEX1 and increases in levels of MSK1 were seen. Overall, these results seem to suggest that BEX1 may protect motor neurons from degeneration, while MSK1 may cause them to be more susceptible to neurodegeneration. Ultimately, these candidate genes may be targeted for gene therapy within these motor neuron populations to confer resistance or reduce susceptibility to the disease, which could provide an effective means of treatment for those affected by ALS.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Molecular Biology, 1954-2017|
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