Stabilization of SODl A4V for identification of drug compounds for therapeutic treatment of Amyotrophic Lateral Sclerosis

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dc.contributor.author Prokupets, Inna
dc.date.accessioned 2014-09-30T18:47:07Z
dc.date.available 2014-09-30T18:47:07Z
dc.date.issued 2010
dc.identifier.uri http://hdl.handle.net/10192/28759
dc.description.abstract Amyotrophic lateral sclerosis (ALS), known as Lou Gehrig's disease, is a fatal, progressive neurodegenerative disease with a median survival post diagnosis of only 3-5 years. This late on-set disease is characterized by the death of brain and spinal cord motor neurons. The only FDA-approved medication, Riluzole, has very limited effects on both patient survival and quality of life. Given this information, it is imperative to develop new strategies to fight the pathology of this debilitating disease. Mutations in the gene-encoding copper/zinc superoxide dismutase ($001) are responsible for approximately 20% of the inherited forms of ALS called fALS and about 2% of total cases. The cause of fALS is understood to be due to a toxic gain-of-function mutation in the SODl protein, which is supported by both dominant inheritance and lack of symptoms in SOD knock-out mice. This toxic gain-of-function suggests a decrease in protein stability and an increase in the likelihood that the fALS variant will aggregate and then lead to disease pathology. The goal of this study is to reduce aggregation of a fALS variant called SODl A4V by either preventing post translation modification of SODl or stabilizing the native SOD1 dimer through cross-linking two symmetric cysteine residues. It was found that compounds ZINC 27780 and ZINC95819 did not stabilize the SOD1 protein. However, it was found that a 3·fold molar excess of cross-linkers BMOE and DTME significantly increased the amount of dimer present. Also, the presence of twice as much BMOE to SODl A4V stabilized the protein by -20 °C.
dc.format.mimetype application/pdf
dc.language English
dc.language.iso eng
dc.publisher Brandeis University
dc.relation.ispartofseries Brandeis University Theses and Dissertations
dc.rights Copyright by Inna Prokupets 2010
dc.title Stabilization of SODl A4V for identification of drug compounds for therapeutic treatment of Amyotrophic Lateral Sclerosis
dc.type Thesis
dc.contributor.department Undergraduate Program in Biology
dc.degree.name BS
dc.degree.level Bachelors
dc.degree.discipline Biology
dc.degree.grantor Brandeis University, College of Arts and Sciences


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