Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder similar to Huntington’s disease (HD), with clinical manifestations including chorea, incoordination, ataxia, and dementia. Both HD and DRPLA are caused by an expansion of a CAG trinucleotide repeat encoding polyglutamine (polyQ) in the atrophin-1 or huntingtin gene. DRPLA and HD cause neuronal dysfunction and cell death in specific areas of the brain with some of the common features and mechanisms thought to underlie pathology and disease progression. These involve abnormal protein conformation, altered protein-protein interactions and the deposition of protein aggregates in the brain. To further evaluate these common features, we have carried out proteomics analysis of DRPLA and HD transgenic models. In addition, we used mass spectroscopy to identify proteins involved in polyglutamine protein complexes in HD and DRPLA cell culture and transgenic models. 2D gel imaging analysis was done using the Amersham Ettan DIGE Dye System and conventional dyes. Mass spectrometry has identified 55 proteins to date. Among these proteins, of particular interest are 7 proteins related to oxidative stress and other forms of stress responses and 4 proteins involved in calcium regulation. Other identified proteins play a role in other neurodegenerative diseases. The possible roles of these proteins in disease progression and pathology will be discussed.
Support Contributed By: NIH grant NS40251A, the Huntington Disease Society of America, Hereditary Disease Foundation and Muscular Dystrophy Association (L.M.E.
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