Retinoic acid receptor-targeted drugs in neurodegenerative disease

ABSTRACTIntroductionNeurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by progressive neuronal loss and currently lack effective treatments that block the degenerative process. It has been suggested that retinoids, a class of vitamin A-derived compounds, may hold potential as future therapeutics for these disorders.Areas coveredIn this review, we explore the role of retinoids in modulating various signaling pathways in the brain which influence pathologically relevant processes such as cellular differentiation, immune and antioxidant response, neurite outgrowth and neurite regeneration. These actions are predominantly mediated by the retinoic acid receptors and we discuss the developmental history of ligands for these receptors, assessing how refinements in receptor binding specificity and improved pharmacokinetic properties may influence the management of off-target effects.Expert opinionNew approaches to understanding retinoid’s mechanisms of action, including non-genomic pathways, and how these mechanisms interact may prove vital in the development of future retinoid-based neurodegenerative disease treatments.