CRTC1 and Huntington disease: However, a recent study showed that brain-specific knockout of Sirt1 resulted in exacerbation of brain pathology in R6/2 mouse model of HD, whereas overexpression of Sirt1 improved survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF), which requires the presence of CREB-regulated transcription coactivator 1 (TORC1; Jeong et al, 2012a).