Hunting the arbiters of neurodegeneration

Abstract

Huntington’s disease (HD) is a member of a group of inherited, progressive but fatal, human neurodegenerative disorders. Diagnosis is based on movement disorders and subcortical dementia and the principal, diagnostic post-mortem feature is the selective degeneration of medium spiny neostriatal neurons and cortical neurons. Degenerating neurons possess filamentous protein inclusions in the nucleus (NIIs) and dystrophic neurites. These NIIs consist predominantly of N-terminal fragments of the disease cognate protein, huntingtin (htt), which possesses increased numbers of repeat glutamine amino acids, or polyglutamine tracts, encoded by CAG nucleotide repeats.