Role of liver X receptor in multiple sclerosis: A long furtive life behind a barrier

Liver X receptors (LXRs) are nuclear receptors that function as transcription factors regulating cholesterol metabolism and are implicated in multiple sclerosis (MS) pathogenesis. This mini-review aims to elucidate the potential role of LXRs in MS neuropathology. MS is the most prevalent inflammatory and demyelinating disease of the central nervous system (CNS), impacting both the brain and spinal cord. Furthermore, alterations in brain cholesterol metabolism in MS can modify the functional activity and immune response of LXRs, which are implicated in MS neuropathology. Dysregulation of LXRs and cholesterol homeostasis is associated with the pathogenesis of MS. LXRs play a critical role in regulating the myelination of nerve sheaths, and defects in LXR function may contribute to the progression of MS. LXRs have immunomodulatory effects, including inhibition of the proliferation of lymphocytes, preventing contact of self-antigens to T cells, and regulating the apoptotic process of T cells. LXRs regulate the activity of microglia, which have pro-inflammatory and anti-inflammatory properties involved in immune regulation and clearance of debris as well as the remyelination process. LXRs regulate the functional activity of glial cells and prevent glial cell-mediated neurodegeneration. LXRs have an important role in the regulation of neuroinflammation during MS neuropathology. LXRs may prevent the progression of neuroinflammation in MS by inhibiting the NF-κB and NLRP3 inflammasome signaling pathways. In conclusion, LXRs play a crucial role in MS neuropathology by mitigating neuroinflammation. These findings proposed that LXR agonists, through modulation of cholesterol homeostasis and inflammatory response, could be effective in the management of MS.