Polyglutamine expansion neurodegenerative disease.

Kennedy's disease was the first of eight neurodegenerative disorders found to be caused by expanded polyglutamine repeats. Each of these disorders is likely caused by a toxic gain of function in the disease gene product, often associated with inclusions of mutant protein in susceptible neurons. The mechanism of toxicity may involve sequestration and depletion of a polyglutamine-containing protein that is important to neuronal survival, such as CREB-binding protein. Recent insights into the biochemistry and cellular pathology of the polyglutamine expansion neurodegenerative diseases provide the opportunity for systematic drug screens and a rational approach to effective therapy.