| Peroxisome Proliferator Activated Receptor Alpha | |
|---|---|
| Gene Symbol | PPARA |
| Full Name | Peroxisome Proliferator Activated Receptor Alpha |
| Chromosome | 22q13.31 |
| NCBI Gene ID | 5465 |
| OMIM | 170998 |
| Ensembl ID | ENSG00000186951 |
| UniProt ID | Q07869 |
| Associated Diseases | Dyslipidemia, Type 2 Diabetes, Alzheimer's Disease, Parkinson's Disease, ALS |
PPARA (Peroxisome Proliferator Activated Receptor Alpha) is a gene encoding a protein involved in metabolic regulation. Located on chromosome 22q13.31, 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 neuroprotective pathways and inflammation.[2] Mutations or dysregulation of PPARA have been implicated in Alzheimer's disease, Parkinson's disease, and metabolic disorders.[3]
PPARA (PPAR-alpha) is a nuclear receptor transcription factor that regulates genes involved in lipid metabolism. It is a ligand-activated receptor that binds fatty acids and fibrate drugs. PPARA plays central roles in peroxisomal and mitochondrial fatty acid oxidation, lipid transport, and inflammation. In the liver, it activates genes involved in fatty acid uptake, beta-oxidation, and ketogenesis. PPARA also has anti-inflammatory effects through transrepression of NF-kB and other inflammatory pathways.
PPARA is implicated in neurodegenerative diseases through its roles in lipid metabolism and inflammation. In Alzheimer's disease, PPARA activation may be beneficial by reducing brain inflammation and enhancing amyloid-beta clearance. Fibrates (PPARA agonists) have shown protective effects in AD models. In Parkinson's disease, PPARA activation protects dopaminergic neurons from oxidative stress and mitochondrial dysfunction. In ALS, PPARA agonists have shown neuroprotective effects in animal models. However, clinical trials have had mixed results.
PPARA is highly expressed in tissues with high fatty acid oxidation including liver, heart, skeletal muscle, and kidney. In the brain, PPARA is expressed in various regions including cortex, hippocampus, and cerebellum. Expression is found in neurons and glial cells, particularly astrocytes. Brain expression is lower than in peripheral tissues but is functionally important.