ARSACS is a devastating neurological disorder caused by the loss of the Sacsin protein. Sacsin knockout (KO) mice recapitulate the cardinal symptoms of ARSACS, and research with these mice could therefore both help understand and ultimately cure the disorder. Mitochondrial dysfunction due to defective mitochondrial fission has been proposed as a primary cause of neurodegeneration in ARSACS. Other evidence suggests that mitochondrial dysfunction may be secondary to cytoskeletal abnormalities.
Our work aims to settle this controversy by crossing Sacs KO mice with mice that lack either positive (PP2A/Bbeta2) or negative (PKA/AKAP1) regulators of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Published and unpublished evidence suggests that both genetic manipulations are likely to influence the progression of the disorder, which we will monitor both behaviorally and with ex vivo imaging techniques. Outcomes from this project will illuminate the role of altered mitochondrial dynamics in ARSACS pathogenesis and point to novel avenues for treatment.
Grant : $71,750 USD
Dr.Stefan Strack, Professor of Pharmacology University of Iowa Carver College of Medicine
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