A possible mechanism through which mutant huntingtin can lead to the downregulation of PGC-1α can be secondary to its effect to enhance the expression [161] and activity of NR2B subunit-containing NMDARs [162], features characteristic of transgenic HD mice [163], which in turn results in a decreased striatal CREB signaling [163], and a subsequent downregulation of PGC-1α [164]. This evidence concerns the gene CREB1 and Huntington disease.