Huntington’s disease (HD) is an incurable illness that causes a progressive loss of coordination and cognitive ability. Patients also develop choreaic (spastic and uncoordinated) movements. HD is one of many neurodegenerative diseases in which a mutant protein accumulates and aggregates in the brain. In the case of HD, the huntingtin protein accumulates in the nucleus and cytoplasm of neurons, thus, one suggested therapeutic strategy is to promote clearance and degradation of this protein. Using primary rat neuron cultures and a transgenic C. elegans model of HD, Jeong et al. demonstrate that acetylation of mutant huntingtin has a neuroprotective effect against toxicity and neurodegeneration. This acetylation improves huntingtin clearance by targeting it for autophagic degradation, thus suggesting a strategy for removing mutant protein in HD.
Jeong H., Then F., Melia T.J. Jr, Mazzulli J.R., Cui L., Savas J.N., Voisine C., Paganetti P., Tanese N., Hart A.C., et al. . (2009). Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 137, 60– 72.
