Retinoids (vitamin A and its metabolites) are regulators of many cellular activities, including cellular growth and differentiation, and they mediate many essential regulatory functions. Biologically active retinoids exert their effects by binding to nuclear retinoic acid receptors (RARA, RARB and RARG), bound to their respective retinoid-X-receptors (RXRA, RXRB and RXRG). Acitretin (trade names Soriatane and Neotigason) is a second-generation synthestic retinoid. It is classed as a keratolytic agent and taken orally in the treament of severe resistant psoriasis. Acitretin is the active metabolite of etretinate and is the retinoid of choice for treating psoriasis because of its more favorable pharmacokinetic profile over etretinate. Despite clinically proven success in treating psoriasis, the mechanism of action of acitretin has not been fully elucidated but it is an agonist for all three subtypes of nuclear retinoic acid receptors, through which it may normalise keratinocyte proliferation, epidermal differentiation and keratinisation (Beckenbach et al. 2015).

ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons (Kuhn et al. 2010), responsible for cleaving amyloid precursor protein (APP) in a non-amyloidogenic manner and producing APPs-alpha, a neuroprotective APP-derived peptide (Mockett et al. 2017, Endres & Deller 2017). Increasing ADAM10 activity may be an attractive target for the treatment of neurodegenerative diseases. However, it must be noted that ADAM10 is also implicated in the ectodomain shedding of NOTCH and ERB2, which can promote cancer progression and inflammatory diseases. Both, RARA and RARB are capable of inducing human ADAM10 promoter activity (Tippmann et al. 2009). In addition, treatment with acitretin (via binding to these receptors) shifts APP processing in AD model mice toward the alpha-secretase cleavage pathway (Tippmann et al. 2009).