Toxic intermediates and protein quality control in the polyglutamine disease, SCA3
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Approved: ___________________________________ Thesis Supervisor ___________________________________ Title and Department ___________________________________ Date ___________________________________ Thesis Supervisor ___________________________________ Title and Department ___________________________________ Date TOXIC INTERMEDIATES AND PROTEIN QUALITY CONTROL IN THE POLYGLUTAMINE DISEASE, SCA3 by Aislinn Joanmarie Williams A thesis submitted in partial fulfillment of the requirements for the Doctor of Philosophy degree in Neuroscience in the Graduate College of The University of Iowa
منابع مشابه
Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro.
Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), is one of at least eight inherited neurodegenerative diseases caused by expansion of a polyglutamine tract in the disease protein. Here we present two lines of evidence implicating the ubiquitin-proteasome pathway in SCA3/MJD pathogenesis. First, studies of both human disease tissue and in vitro models showed redist...
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Spinocerebellar ataxia type 3 (SCA3) is a currently incurable neurodegenerative disorder caused by a CAG triplet expansion in exon 10 of the ATXN3 gene. The resultant expanded polyglutamine stretch in the mutant ataxin-3 protein causes a gain of toxic function, which eventually leads to neurodegeneration. One important function of ataxin-3 is its involvement in the proteasomal protein degradati...
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Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ATXN3 gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show tha...
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Spinocerebellar ataxia type-3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine repeat expansion in the ataxin-3 protein. Cleavage of mutant ataxin-3 by proteolytic enzymes yields ataxin-3 fragments containing the polyglutamine stretch. These shorter ataxin-3 fragments are thought to be involved in SCA3 pathogenesis due to their increased cellular toxicity and their involvement i...
متن کاملA knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript.
Polyglutamine diseases, including spinocerebellar ataxia type 3 (SCA3), are caused by CAG repeat expansions that encode abnormally long glutamine repeats in the respective disease proteins. While the mechanisms underlying neurodegeneration remain uncertain, evidence supports a proteotoxic role for the mutant protein dictated in part by the specific genetic and protein context. To further define...
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تاریخ انتشار 2016