Help for Huntington's: Stem cells for neurodegenerative disease

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder that most commonly starts in the third to fifth decade of life and is caused by the mutation of a single gene. The mutation is an expansion of a CAG repeat region in exon one of the huntingtin gene. Normally there are fewer than 36 such repeats, and more than 39 makes the onset of disease certain, providing that the individual does not die of other causes. The extended CAG repeat is translated into the huntingtin protein as an extended polyglutamine stretch in the N-terminal domain of the protein. The effect of the mutated protein is to produce progressive dysfunction and degeneration of CNS (central nervous system) neurons, predominantly in the striatum. The striatum, which is one component of a group of CNS nuclei termed the 'basal ganglia', is important for the proper execution of movement and is also involved in cognition (particularly through its connections with the frontal cortex) and in aspects of behaviour. Consequently, HD patients display motor abnormalities (including involuntary movements such as chorea and dystonia, slowing and poverty of movement, incoordination, loss of balance, difficulty swallowing and slurred speech), a progressive frontal-lobe-like dementia, and psychiatric symptoms (such as irritability, depression and anxiety). © 2006 Biochemical Society.