Chapter 2 Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies

Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 144 Author(s): Christopher A. Ross, Martin Kronenbuerger, Wenzhen Duan, Russell L. Margolis The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and mutant huntingtin (htt) protein; gene expression profiles in HD cells and tissue; the neurotoxicy of mutant htt RNA; and the expression of an antisense transcript from the HD locus. We conclude that rationale therapeutics for HD is within sight, though many questions remain to be answered.
Source: Handbook of Clinical Neurology - Category: Neurology Source Type: research