The novel function of bexarotene for neurological diseases.

Abstract

Bexarotene, a retinoid X receptor (RXR) agonist, is approved by FDA to treat cutaneous T-cell lymphoma. However, it has also demonstrated promising therapeutic potential for neurological diseases such as stroke, traumatic brain injury, Parkinson's disease, and particularly Alzheimer's disease(AD). In AD, bexarotene inhibits the production and aggregation of amyloid β (Aβ), activates Liver X Receptor/RXR heterodimers to increase lipidated apolipoprotein E to remove Aβ, mitigates the negative impact of Aβ, regulates neuroinflammation, and ultimately improves cognitive function. For other neurological diseases, its mechanisms of action include inhibiting inflammatory responses, up-regulating microglial phagocytosis, and reducing misfolded protein aggregation, all of which aid in alleviating neurological damage. Here, we briefly discuss the characteristics, applications, and adverse effects of bexarotene, summarize its pharmacological mechanisms and therapeutic results in various neurological diseases, and elaborate on the problems encountered in preclinical research, with the aim of providing help for the further application of bexarotene in central nervous system diseases.