Transcellular regulation of the proteostasis network in Kennedy’s disease
Summary: Misfolding and abnormal accumulation of the mutant androgen receptor in Kennedy’s disease indicates that the cellular machinery controlling protein abundance, folding, and transport (proteostasis) may be defective in the disease. We are planning to study molecular mechanisms of Kennedy’s disease in the worm Caenorhabditis elegans. For this, we will genetically engineer worms to express the mutant androgen receptor in the neuromuscular system and assess effects of the polyglutamine expansion on proteostasis regulation in this model organism. Insights into cell type-specific effects and regulation across tissues may lead to new therapeutic approaches for this disease.
