A2A Adenosine Receptor Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-protein
Protein Name: Adenosine A2a receptor
Gene: ADORA2A
UniProt ID: P29274
PDB ID: 5UIG, 3EML
Molecular Weight: ~44 kDa
Subcellular Localization: Plasma membrane, lipid rafts
Protein Family: G protein-coupled receptor (class A), adenosine receptor family
::
A2A ADENOSINE RECEPTOR is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of A2A ADENOSINE RECEPTOR is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
The adenosine A2a receptor (A2AR) is a seven-transmembrane GPCR with an extracellular N-terminus and intracellular C-terminus. The receptor contains:
- Seven transmembrane helices (TM1-TM7)
- Three extracellular loops (ECL1-ECL3)
- Three intracellular loops (ICL1-ICL3)
- Orthosteric adenosine binding site within the transmembrane bundle
Crystal structures have revealed the inactive and active conformations, providing insights into GPCR signaling and drug binding.
A2AR couples to Gs/olf proteins, stimulating adenylate cyclase activity and increasing intracellular cAMP levels. In the brain:
- Striatal function: A2AR is highly expressed in the striatum where it modulates dopamine D2 receptor (D2R) signaling through heteromeric receptor complexes
- Motor control: A2AR activation promotes locomotion; antagonism reduces motor inhibition
- Neuroinflammation: A2AR on microglia and astrocytes modulates inflammatory responses
- Sleep regulation: A2AR in the basal forebrain promotes wakefulness
- Cardiovascular: Peripheral A2AR causes vasodilation
A2AR is a major therapeutic target in PD. A2AR antagonists (caffeine, istradefylline) improve motor function by:
- Blocking A2AR-D2R negative allotropic interactions
- Reducing excessive inhibition of the direct pathway
- Modulating neuroinflammation
- Upregulation of A2AR in the striatum contributes to motor dysfunction
- A2AR antagonists may provide neuroprotection
- A2AR-D2R interaction affects psychosis phenotypes
- Genetic variants influence disease risk and treatment response
| Drug |
Type |
Clinical Status |
Indication |
| Istradefylline |
Antagonist |
Approved (Japan) |
Parkinson's disease |
| Caffeine |
Antagonist |
Over-the-counter |
PD prevention |
| Preladenant |
Antagonist |
Discontinued |
Parkinson's disease |
| Tozadenant |
Antagonist |
Discontinued |
Parkinson's disease |
- 10954653: A2AR-D2R heteromerization. Nature. 2000.
- 15653700: A2AR antagonists in PD. Lancet Neurol. 2005.
- 19158675: Caffeine and PD risk. JAMA. 2009.
- 25080937: A2AR structure. Nature. 2014.
The study of A2A Adenosine Receptor Protein 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.
- Chen JF, et al. Adenosine A2A receptors: A major target for neuroprotection. Journal of Parkinson's Disease. 2020. PMID:32333542
- Kase D, et al. A2A adenosine receptor and Parkinson's disease: New strategies. Neuropharmacology. 2019. PMID:31284019
- Wei CJ, et al. A2A receptors in basal ganglia and stroke. Brain Research. 2019. PMID:30683274
- Jenner P, et al. A2A antagonists as novel anti-parkinsonian agents. Movement Disorders. 2020. PMID:32851782
- Yu L, et al. Adenosine A2A receptors in neuroinflammation. Neurobiology of Disease. 2021. PMID:33775628
- Schwarzschild MA, et al. Targeting A2A receptors for neuroprotection in PD. Lancet Neurology. 2019. PMID:31003866
- Morelli M, et al. A2A adenosine receptor antagonism and levodopa-induced dyskinesia. Brain. 2018. PMID:29465074
- Cieśla M, et al. A2A receptor blockade in models of neurodegeneration. Pharmacological Reviews. 2019. PMID:31164370