Adra2C Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ADRA2C Gene is an important protein/gene involved in various neurological processes. This page provides comprehensive information about its structure, function, and role in neurodegenerative diseases.
The ADRA2C gene encodes the alpha-2C adrenergic receptor (α2C-AR), a G protein-coupled receptor that mediates sympathetic tone inhibition. The α2C subtype is widely expressed in the central nervous system and peripheral tissues, playing crucial roles in regulating norepinephrine signaling, autonomic function, and stress responses. The receptor is unique among α2-AR subtypes for its distinctive subcellular distribution and functional properties.
| Attribute |
Value |
| Gene Symbol |
ADRA2C |
| Full Name |
Adrenoceptor Alpha 2C |
| Chromosomal Location |
4p16.3 |
| Gene ID |
152 |
| Ensembl ID |
ENSG00000141449 |
| UniProt ID |
P21917 |
| Aliases |
α2C-AR, ADRA2C |
ADRA2C encodes a 462-amino acid GPCR with characteristic features:
¶ Transmembrane Domain
- 7 TM Helices (TM1-TM7): Canonical GPCR structure
- Disulfide Bond: Conserved cysteine in extracellular loop 2
- N-linked Glycosylation Sites: N-terminal extracellular domain
¶ Functional Domains
- N-terminus: Extracellular, glycosylated
- Extracellular Loops: Ligand binding (minor)
- Transmembrane Core: Major ligand binding site
- Cytoplasmic Tail: G protein coupling, phosphorylation sites
Alpha-2C adrenergic receptor has distinct signaling properties:
- Primary: Gi/o protein coupling
- Adenylate Cyclase Inhibition: Reduces cAMP production
- GIRK Channel Activation: Hyperpolarizes neurons via potassium efflux
- MAPK Pathways: Can activate alternative signaling cascades
- Agonists: Norepinephrine, epinephrine, clonidine, dexmedetomidine
- Antagonists: Yohimbine, rauwolscine, idazoxan
- Desensitization: GRK-mediated phosphorylation
- Internalization: Arrestin-dependent
- Sympathetic Inhibition: Reduces sympathetic outflow
- Neuronal Inhibition: Hyperpolarizes postsynaptic neurons
- Presynaptic Autoreceptor: Regulates norepinephrine release
- Thermoregulation: Cutaneous vasoconstriction
- Analgesia: Spinal α2C-AR in pain modulation
- Sedation: Central sedative effects
- Cerebral Cortex: Layer-specific expression
- Hippocampus: CA1-CA3 regions
- Basal Ganglia: Striatum, substantia nigra
- Spinal Cord: Dorsal horn (pain transmission)
- Locus Coeruleus: Noradrenergic cell bodies
- Hypothalamus: Neuroendocrine regulation
- Platelets: Platelet aggregation regulation
- Adipose Tissue: Lipolysis regulation
- Vasculature: Vascular tone
- Pancreas: Insulin secretion modulation
- Altered α2C-AR expression in AD brain
- Contributes to noradrenergic dysfunction
- Loss of cortical α2C-AR in early AD
- Potential therapeutic target
- Interaction with amyloid pathology
- Dysregulated α2-AR signaling in PD
- Altered autonomic function
- May affect levodopa response
- α2-AR antagonists in PD psychosis
- Blunted hypothermic response
- α2-AR antagonists (yohimbine) have antidepressant effects
- Dysregulated receptor function in depression
- Noradrenergic hypothesis of depression
- Therapeutic targeting
- Anxiety Disorders: α2C-AR role in fear/stress responses
- Pain: Spinal α2C-AR in analgesia
- Hypertension: Peripheral α2C-AR in blood pressure
- Metabolic Disorders: Effects on insulin secretion
| Drug |
Type |
Application |
| Clonidine |
Agonist |
Hypertension, ADHD |
| Dexmedetomidine |
Agonist |
Sedation, analgesia |
| Yohimbine |
Antagonist |
Depression, orthostatic hypotension |
| Brimonidine |
Agonist |
Glaucoma |
- α2C-AR modulation for cognitive enhancement
- Selective antagonists for depression
- Pain management strategies
- Developing subtype-selective ligands
- Understanding α2C-AR in neurodegeneration
- Gene therapy approaches
The study of Adra2C Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- PMID:8835713 - Cloning of ADRA2C
- PMID:11099489 - α2C-AR in thermoregulation
- PMID:16446404 - Adrenergic receptors in AD
- PMID:24993950 - α2-AR in PD
- PMID:18468979 - α2C-AR structure
- PMID:20379642 - G protein coupling
- PMID:23774212 - α2-AR in depression
- PMID:26113720 - Therapeutic targeting