Grant: Project Grant

In recent years the research community has grown to appreciate the importance of the small "micro-RNA" molecules in human health and disease. These molecules control various biological processes by adjusting protein levels in the cell. As such, any imbalance in microRNA levels can be disastrous for the organism. Interestingly, we and other have identified a number of microRNAs that are disturbed in neurodegenerative disorders, including Huntington's disease (HD). While we know that HD is caused by a genetic mutation in the Huntingtin (Htt) gene, it remains uncertain how the brain cells go awry and die. Interestingly, microRNA-132 is severely reduced in the brain of HD individuals. Our studies in mice demonstrate that microRNA-132 loss leads to abnormal Htt and brain cell function. In this project, we aim to better understand the role and therapeutic potential of microRNA-132 in HD. We anticipate that the reintroduction of microRNA-132 into the brain will be highly beneficial for patients. We will test this hypothesis in recognized HD mouse models, and study in parallel how microRNA-132 (and Htt) is involved in cell loss in mice and humans. Once completed, these experiments will provide important information for the understanding of HD pathogenesis and development of microRNA-based drugs for HD.