Recently, specific overexpression of MKP-1 was shown to exert neuroprotective effects against mHTT through inhibition of JNK and p38.80 Pharmacological MLK2 inhibition reduced toxicity in several model systems and increased motor performance and BDNF levels in the R6/2 mouse.81 Small-molecule approaches to activate MKP-1 and ERK, or to inhibit MLK2, JNK, and p38, may be of value, but these pathways, their role in HD, and the optimal targets and means of modulating them are incompletely understood. This evidence concerns the gene MAPK8 and Huntington disease.