Moreover, epidermal keratinocytes are not only able to release biologically relevant amounts of this endogenous opioid, but they can do it in response to a wide variety of “AD-relevant” and other stimuli, including CRH, ET-1, IL-31, CB2 activation, UVB and blue light irradiation, or TPA treatment (Figure 5). This evidence concerns the gene EDN1 and Alzheimer disease.