Huntingtin and the molecular pathogenesis of Huntington's disease
Summary
Fourth in Molecular Medicine Review Series
Huntington's disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review, we outline the potential functions of htt as defined by the proteins with which it has been found to interact. We then focus on evidence that supports a role for transcriptional dysfunction and impaired protein folding and degradation as early events in disease pathogenesis.
Acknowledgments
We apologize to our colleagues whose work could not be cited, or was cited indirectly, due to space limitations. We thank members of the Neurogenetics Laboratory for advice and comments on the manuscript.