HOW COULD RETINOIDS FIT INTO ALZHEIMER'S THERAPY?

Retinoids are a class of natural and synthetic molecules structurallyand/or functionally related to all-trans-retinoic acid (ATRA), a metabo-lite of vitamin A (retinol). The retinoid system controls the expression ofhundreds of genes, including transcription factors, enzymes, structuralproteins, cell surface receptors, neurotransmitters, hormones andgrowth factors, hence modulating cell proliferation, differentiation,morphogenesis and immunity. The retinoid-associated signaling playsa critical role in neurodevelopment and remains active in the adult cen-tral nervous system, thus assuming high relevance in the context ofneurodegeneration. The ability of retinoids to exert antioxidant effects,decrease -amyloid (A) accumulation, improve neurotransmission,suppress neuroinflammation and promote neural regeneration is dis-cussed. Although retinoids with their pleiotropic activity are revealing apromising approach for the management of Alzheimer’s disease (AD),timing as well as appropriate dosage and safety still remain a chal-lenge. In particular, assuming that the end-stage lesions (senileplaques and neurofibrillary tangles) are an adaptive response to oxida-tive stress underlying AD, late administration of retinoids could para-doxically suppress a protective mechanism by inhibiting Adeposits.