Liver X Receptors in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential

Liver X receptors (LXRs), comprising LXRα and LXRβ, are oxysterol-responsive nuclear receptors that regulate cholesterol homeostasis and inflammatory signaling. In the central nervous system (CNS), LXR activity influences amyloid-β metabolism, glial responses, synaptic integrity, myelination, and blood–brain barrier function. This narrative review synthesizes shared and disease-specific mechanisms across neurodegenerative and demyelinating disorders, distinguishing established experimental effects from proposed pathways. We compare representative LXR modulators by receptor and transcriptional selectivity, CNS exposure, efficacy, and safety. Particular attention is given to hepatic lipogenesis caused by systemic LXRα activation and to LXRβ-selective or function-selective ligands, brain-targeted delivery, combination strategies, and biomarker-guided patient stratification. Although preclinical findings support therapeutic potential, clinical efficacy remains unproven. Priorities include cell-type-specific causal validation, quantitative CNS target engagement, and long-term safety assessment.