| Nuclear Receptor Subfamily 1 Group H Member 3 | |
|---|---|
| Gene Symbol | NR1H3 |
| Full Name | Nuclear Receptor Subfamily 1 Group H Member 3 |
| Chromosome | 11p11.2 |
| NCBI Gene ID | 10062 |
| OMIM | 603711 |
| Ensembl ID | ENSG00000125448 |
| UniProt ID | Q9GZN5 |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Atherosclerosis, Multiple Sclerosis |
NR1H3 (Nuclear Receptor Subfamily 1 Group H Member 3) is a gene encoding a protein involved in metabolic regulation. Located on chromosome 11p11.2, this gene encodes a protein that plays important roles in lipid metabolism, energy homeostasis, and transcriptional regulation.[1] The gene is expressed in multiple tissues including brain, where it is involved in cellular signaling.[2] Mutations or dysregulation of NR1H3 have been implicated in neurodegenerative diseases.[3]
NR1H3 (LXR-alpha) is a nuclear receptor that functions as a transcription factor. It is a ligand-activated receptor that binds oxysterols and regulates genes involved in cholesterol metabolism, lipid transport, and inflammation. LXR-alpha plays important roles in reverse cholesterol transport, fatty acid synthesis, and glucose metabolism. It forms heterodimers with RXRA and binds to LXR response elements (LXREs) in target genes. LXR activation leads to upregulation of cholesterol efflux genes including ABCA1 and ABCG1.
NR1H3/LXR-alpha is implicated in neurodegenerative diseases through its roles in cholesterol metabolism and neuroinflammation. In Alzheimer's disease, LXR activation promotes amyloid-beta clearance through upregulation of ABCA1 and ABCG1, which enhance apolipoprotein-mediated cholesterol efflux. LXR agonists have shown protective effects in AD mouse models. In Parkinson's disease, LXR activation may protect dopaminergic neurons from oxidative stress. LXR also has anti-inflammatory effects in glial cells. LXR beta (NR1H2) is also important in the brain.
NR1H3 is highly expressed in metabolically active tissues including liver, intestine, kidney, and adipose tissue. In the brain, it is expressed in cortex, hippocampus, and other regions. Expression is found in neurons and glial cells including astrocytes and microglia. Brain expression of NR1H3 is lower than in liver but is functionally significant.