CLEAVAGE, AGGREGATION AND TOXICITY OF THE EXPANDED ANDROGEN RECEPTOR IN SPINAL AND BULBAR MUSCULAR-ATROPHY

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disea se caused by the expansion of a polyglutamine repeat within the androg en receptor (AR), We have studied the mutant AR in an in vitro system, and find both aggregation and proteolytic processing of the AR protei n to occur in a polyglutamine repeat length-dependent manner, In addit ion, we find the aberrant metabolism of expanded repeat AR to be coupl ed to cellular toxicity, indicating a likely molecular basis for the t oxic gain of AR function that produces neuronal degeneration in SBMA.