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.
Fischbeck
K H
KH
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1250, USA. kf@codon.nih.gov
D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
D010455:Peptides; C097188:polyglutamine