Retinoids for treatment of Alzheimer's disease

Abstract

Retinoids are Vitamin A derivatives involved in cellular regulatory processes including cell differentiation, neurite outgrowth and defense against oxidative stress. Retinoids may also influence Amyloid beta processing upregulation of alpha secretase via ADAM10. Vitamin A and other retinoids also directly inhibit formation of Amyloid fibrils in vivo. These properties of retinoids are relevant to theories of Alzheimer's disease pathogenesis. Retinoids are already used in treatment of acne vulgaris, psoriasis, neuroblastoma and acute promyelocytic leukemia. Clinical studies involving in cognitively impaired older adults with Alzheimer's disease are beginning with a variety of retinoids. These studies need to address safety issues of retinoids in older populations, and hold hope for demonstrating efficacy in translating these basic mechanisms to treatment of a widespread dementing illness.

All-trans-retinoic Acid Reduces BACE1 Expression under Inflammatory Conditions via Modulation of Nuclear Factor κB (NFκB) Signaling

“…These effects were largely reversed by the administration of RA (29,30). Taken together, these data provide strong rationale investigating RA-based therapy in AD (31)(32)(33)(34).…”

“…To test our hypothesis, we examined the expression of BACE1 in atRA-treated Tg2576, high fat diet, and LPS-challenged mice. These conditions have all been reported to induce inflammatory events in the brain (34,37,38). We further investigated the underlying molecular mechanism using in vitro cultured rat primary neurons.…”

Transthyretin: a multifaceted protein

“…It also modulates neurogenesis, neuronal survival and synaptic plasticity in hippocampus, olfactory bulb and hypothalamus (61). Retinoids can regulate cell differentiation, neurite outgrowth and protection against oxidative stress (62). Several studies suggest vitamin A as a possible therapeutic agent in Alzheimer disease (AD): (i) the disruption of retinoid signaling induced deposition of Aβ in the cerebral blood vessels (63); (ii) vitamin A inhibited amyloid fibril formation (64) and (iii) in vivo studies revealed that administration of vitamin A decreased Aβ deposition and improved spatial learning and memory (65).…”

All-<b><i>trans</i></b>-Retinoic Acid Modulates Nitric Oxide and Interleukin-17A Production by Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease

“…Retinoic acids (RAs) are bioactive metabolites of retinoids (vitamin A derivatives) [27] that regulate a wide range of biological processes, including vision, cellular proliferation, differentiation, and embryogenesis [28,29]. RAs have been traditionally considered to be antioxidant compounds [30] and have attracted the attention of researchers because of their additional anti-inflammatory and immunomodulatory functions [31].…”