Identification of New Polyglutamine-Specific Mutant AR-Interacting Proteins in SBMA Motor Neurons
Summary: Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive neuromuscular disease. As the disease proceeds, nerve cells in the spinal cord (called motor neurons) start to die and muscle cells will waste away. The causative mutation of SBMA is the mutant androgen receptor (AR) with an abnormal expansion in the certain region. Such aberrant expansion in the mutant protein (called a polyglutamine tract) damages the normal function of the protein as well as obtains toxicity. Thus, it is important to understand how the mutant AR is regulated via other proteins in the disease. Here, I propose to use a human induced pluripotent stem cell model to generate disease-relevant motor neuron-like cells, and use these cells to identify specific interacting proteins of the mutant androgen receptor. I am hoping that my research will help provide a motor neuron-specific basis for designing and developing novel therapeutics for the treatment of SBMA.
