How could retinoids fit into Alzheimer's therapy?

Retinoids are a class of natural and synthetic molecules structurally and/or functionally related to all-trans-retinoic acid (ATRA), a metabolite of Vitamin A (retinol). The retinoid system controls the expression of hundreds of genes, including transcription factors, enzymes, structural proteins, cell surface receptors, neurotransmitters, hormones and growth factors, hence modulating cell proliferation, differentiation, morphogenesis and immunity. The retinoid-associated signaling plays a critical role in neurodevelopment and remains active in the adult central nervous system, thus assuming high relevance in the context of neurodegeneration. The ability of retinoids to exert antioxidant effects, decrease β-amyloid (Aβ) accumulation, improve neurotransmission, suppress neuroinflammation and promote neural regeneration is discussed. Although retinoids with their pleiotropic activity are revealing a promising approach for the management of Alzheimer's disease (AD), timing as well as appropriate dosage and safety still remain a challenge. In particular, assuming that the end-stage lesions (senile plaques and neurofibrillary tangles) are an adaptive response to oxidative stress underlying AD, late administration of retinoids could paradoxically suppress a protective mechanism by inhibiting Aβ deposits.