It is plausible that the downregulation of TCF4 could be one of the causal mechanisms underlying the downregulation of BDNF expression in the hippocampus and cerebral cortex of HD mouse models and patients in addition to the well-described NRSF-dependent mechanism (Zuccato et al., 2001, 2003, 2007; Conforti et al., 2013). The gene discussed is REST; the disease is Huntington disease.