Huntington's disease (HD) is a progressive neurodegenerative disease caused by a glutamine expansion within huntingtin protein. The exact pathological mechanisms determining disease onset and progression remain unclear.
Aggregated polyglutamines constitute a biomarker for mutant huntingtin useful for developing therapeutics. A small molecule, C2-8, inhibits polyglutamine aggregation in cell culture and brain slices and rescues degeneration of photoreceptors in a Drosophila model of HD.C2-8-treated mice showed improved motor performance and reduced neuronal atrophy and had smaller huntingtin aggregates.C2-8 provides an essential tool to help elucidate mechanisms of neurodegeneration in HD and a therapeutic lead for further optimization and development.
Ratnakar