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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Dr. John M. Warrick
There are nine known Polyglutamine diseases that are caused by an expansion in the Polyglutamine [Poly Q] tract in related proteins (Sugars et al., 2004). Machado-Joseph Disease [MJD] is the most common of these diseases. MJD, like the rest of the Poly Q diseases, is an autosomally inherited dominant disorder caused by a trinucleotide [CAG] repeat expansion (Ichikawa et al., 2001). This abnormally long glutamine tract Poly Q expansion within the MJD protein [Ataxin-3] causes a deleterious gain-of-function inducing protein toxicity (Ichikawa et al., 2001). The toxicity of the mutant expanded Ataxin-3 protein has been linked to misfolding and oligomerization (Gales et al., 2005). Also all Poly Q diseases are characterized by a buildup of disease proteins and intra-neuronal protein aggregates (Sugars et al., 2004). In MJD this accumulation of mutant Ataxin-3 protein eventually leads to the degeneration and death of cells in certain parts of the brain involved in motor function. This eventually leads to the death of the patient. The areas of the brain most significantly affected in MJD are the cerebellum and brain stem [Fig. 1].
Sorace, Brian James, "Investigation of CREB binding protein as a potential therapy in the creation of a novel proteomic profile for human neurodegenerative disease Spinocerebellar Ataxia type III/Machado-Joseph Disease" (2011). Honors Theses. 119.