Huntingtin protein: A new option for fixing the Huntington's disease countdown clock

Huntington's disease is a dreadful, incurable disorder. It springs from the autosomal dominant mutation in the first exon of the HTT gene, which encodes for the huntingtin protein (HTT) and results in progressive neurodegeneration. Thus far, all the attempted approaches to tackle the mutant HTT-induced toxicity causing this disease have failed. The mutant protein comes with the aberrantly expanded poly-glutamine tract. It is primarily to blame for the build-up of P-amyloid-like HIT aggregates, deleterious once broadened beyond the critical similar to 35-37 repeats threshold. Recent experimental findings have provided valuable information on the molecular basis underlying this HIT-driven neurodegeneration. These findings indicate that the poly-glutamine siding regions and many post-translation modifications either abet or counter the poly-glutamine tract. This review provides an overall, up-to-date insight into HTT biophysics and structural biology, particularly discussing novel pharmacological options to specifically target the mutated protein and thus inhibit its functions and toxicity. (C) 2018 Elsevier Ltd. All rights reserved.