Given the therapeutic role of PACAP in HD, and SP1 as a key transcription factor for Htt expression [28], it was hypothesized that PAMs of PAC1-R, such as SPAM1, exert neuroprotective effects by interfering with the binding of NRSF through upregulating the expression of Htt by inducing nuclear translocation of the fragments of PAC1-R. Here, HTT is linked to Huntington disease.