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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Biochemistry & Molecular Biol.
Dr. John M. Warrick
Machado Joseph disease, also known as Spinocerebellar Ataxia Type 3 (MJD/SCA3), is the most common fatal dominantly inherited ataxia and is the most frequent neurodegenerative disease caused by polyglutamine (polyQ) encoding CAG repeat expansion (Arrasate, 2004). In MJD/SCA3, the disease causing gene is MJD1/ATX3 on chromosome 14. The normal form of the gene has a normally occurring CAG repeat length of less than 36 repeats (Kawaguchi, 1994). The CAG codon codes for glutamine and causes a natural glutamine repeat in the subsequent protein. Expansion to greater than 50 CAG’s causes an expansion of the natural glutamine repeat and a toxic gain of function in the protein (Kawaguchi, 1994). It is believed these expanded repeats cause a protein to become toxic because the inter and intramolecular forces between amino acid side chains and backbone cause a change in the protein structure which in turn drastically changes the resulting secondary, tertiary and quaternary structure of the protein, causing neuronal dysfunction and loss (Nucifora, 2001). This misfolding does not only affect the mutated protein, but can also affect many downstream products (Figure 1).
Simmelink, Andrew Lawrence, "Determination of CREB binding protein levels and an examination of proteomic profiles in the drosophila model of the human neurodegenerative disease Spinocerebellar ataxia type III / Machado-Joseph disease" (2011). Honors Theses. 124.