DNA Repair in Dystonia
Abstract
Dystonia has been defined as a syndrome of involuntary, sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements, or abnormal postures. Dystonia without associated movement or neurological disorders has been termed "isolated dystonia." Dystonia is a relatively common movement disorder that can affect children, young adults, and the elderly. Genetic risk factors and environmental factors contribute to the development of dystonia. Extreme repetitive use of specific muscles groups and peripheral trauma are known triggers of dystonia. Several genes associated with dystonia appear to be involved in cellular pathways that repair damaged deoxyribonucleic acid (DNA). It is well-known that radiation exposure can cause breaks in DNA. We hypothesize that (1) intense repetitive motor activity can also induce DNA breaks within regions of the brain implicated in the development of dystonia, and (2) genetic defects associated with dystonia result in defective repair of DNA. The proposed experiments will utilize genetically engineered mice that harbor mutations known to cause dystonia in humans. Our proposed experiments will, for the first time, link an environmental trigger (repetitive motor activity) to the root cause of dystonia and provide the groundwork to limit DNA breaks in people at risk for dystonia and identify treatments to facilitate repair of DNA.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710062
Entities
People
- Mark S LeDoux
Organizations
- United States Army
- University of Tennessee Health Science Center