Torsion Dystonia and TorsinA

TorsinA is a novel AAA+ protein identified in the search for mutations underlying the hereditary movement disorder, early onset torsion dystonia. We have conducted preliminary biochemical analyses of torsinA and its dystonia-related counterpart in cultured cells and are now beginning to focus more exclusively on functional studies in primary neurons. A major goal of these efforts is to evaluate neuronal signaling in cultured neurons following overexpression of wild-type and mutant torsinA, given that patients with dystonia display altered brain activity in various regions during motor tasks. Two approaches are currently being pursued: overexpression of mutant and wild-type torsinA in cultured neurons by novel viral vectors; and establishment of primary neuronal cultures from transgenic mice overexpressing human mutant and wild-type torsinA. Using these strategies we hope to identify possible clues as to the normal function of torsinA as well as the physiological consequences of the dystonia-related mutation.