Saturday, February 18, 2017
Exhibit Hall (Hynes Convention Center)
Lance Heady, University of Iowa, Iowa City, IA
Protein aggregation is a major pathologic component of polyglutamine (polyQ) neurodegenerative diseases, such as Huntington’s disease (HD). HD, a genetic disorder of progressive dysfunction and death of nerve cells in the brain, leads to abnormal and involuntary movement, cognitive dysfunction, depression, and death. An expanded PolyQ chain in the huntingtin protein drives the disease pathology. HD manifests when an individual has more than the 40-glutamine repeats within the Huntingtin gene, with greater number of repeats correlating with earlier onset and increased disease severity. No treatments to slow the progressive neurodegeneration in HD are currently available. The P7C3-class of neuroprotective molecules potently block neuronal cell death in pre-clinical models of neurodegeneration, including Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and traumatic brain injury. Here, we examine the efficacy of P7C3 neuroprotective compounds in Caenorhabditis elegans (C. elegans) and a HeLa cell model of HD. Both models mimic the human disease with glutamine repeats above the 40-glutamine threshold that precipitate protein aggregation. The C. elegans model also have aggregation-associated behavioral deficits. Utilization of biochemical and behavioral tests allow for the investigation of the protective efficacy of P7C3 compounds in these outcome measures. Currently no treatments slow the progression of HD and treat the underlying disease pathology. HD currently afflicts approximately 200,000 individuals worldwide. The overall goal is to foster development of new treatment strategies for patients suffering from HD.