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Date of Award


Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science




Machado-Joseph Disease (Spinocerebellar ataxia type 3) is a fatal human neurodegenerative disease with no current cure or effective therapy. It is caused by a CAG repeat expansion in the gene coding for the ATX3 protein, resulting in the expansion of the polyglutamine domain. There are currently nine other neurological polyglutamine diseases that result from a CAG repeat, including Huntington’s disease. ATX3 is a 42 KDa protein encoded by the MJD1 gene (ATXN3) that is widely expressed in the central nervous system and is a unique deubiquitinating enzyme that is involved in a ubiquitin-proteasome pathway and a lysosomeautophagy pathway that both degrade proteins (Paulson, 2012). MJD is dominantly inherited and is the most common form of dominantly inherited ataxia with homozygous individuals displaying increased disease progression and degeneration (Lerer et al, 1996). This CAG expansion confers a toxic gain of function to the protein causing misfolding and the accumulation of nonfunctioning aggregates which lead to the degeneration of motor associated neurons in the brain. There are three clinical types of MJD: type 1, characterized by disease onset early in life around 25 years; type 2, the most common type beginning in mid adult years, and type 3, late onset form showing symptoms around 50 years of age (Paulson, 2012).