Liver X receptors: A therapeutic target in demyelinating disorders

Abstract

Liver X Receptors (LXRα and LXRβ) are nuclear receptors that regulate various metabolic processes via transcriptional regulation, including lipid and cholesterol homeostasis. Recent evidence highlights the involvement of LXR activation in myelin synthesis and maintenance. Given the essential role of myelin in neuronal communication, its loss in disorders such as multiple sclerosis and Alzheimer's disease underlines the urgent need for effective remyelinating therapies. Restoring the functions of oligodendrocytes to stimulate remyelination offers an interesting approach to protect neurons and slow down neurodegeneration. LXRs have been suggested as potential therapeutic targets in demyelinating disorders as they can promote cholesterol turnover and reduce inflammation, creating a favorable environment for remyelination. Furthermore, activation of LXR directly enhances remyelination by inducing myelin genes. Since various literature and research describe the potential neuroprotective and (re)myelinating benefits of LXR, this review discusses the role of the LXR pathway in (re)myelinating strategies. It highlights the pharmacological compounds for LXR activation, as well as naturally occurring LXR agonists with potential therapeutic value for promoting remyelination.

Keywords: (Re)myelination; Demyelinating disorders; Liver X receptors; Pharmacological compounds; Plant-based compounds.