The GABA-A receptor is a pentameric structure typically composed of combinations of α, β, and γ subunits. The α2 subunit (GABRA2) is predominantly expressed during early neurodevelopment and remains functional in specific brain regions, including the hippocampus and cerebral cortex . Antibodies like AGA-002 (Alomone Labs) and ab307359 (Abcam) bind to extracellular or intracellular epitopes of this subunit, enabling precise localization studies .
GABRA2 antibodies are widely used in:
Western Blotting: Detects endogenous α2 subunits in brain lysates .
Immunohistochemistry: Maps receptor distribution in brain tissues (e.g., rat hippocampus) .
Functional Studies: Investigates GABA-A receptor trafficking and synaptic clustering .
Alomone Labs AGA-002: Validated in immunoprecipitation assays, confirming specificity for α2 subunits in cerebral cortex samples .
Abcam ab307359: Demonstrates cytoplasmic staining in hippocampal neurons via immunofluorescence .
Autoantibodies against GABA-A receptor subunits, including α2, are implicated in neurological disorders:
While no direct therapies target α2 subunits, modulating GABAergic signaling remains a focus:
Clazakizumab Trials: Anti-IL-6 therapies show potential in antibody-mediated disorders .
GABAergic Drugs: Preclinical studies suggest α2-specific agonists/antagonists could treat neuropsychiatric conditions .
Combine orthogonal methods:
Implement quality control metrics:
| Parameter | Validation Method | Acceptance Criteria |
|---|---|---|
| Binding affinity | SPR/BLI kinetics | KD ≤ 10 nM |
| Specificity | Western blot vs. recombinant panel | ≤5% cross-reactivity |
| Functional activity | Cell-based neutralization assay | IC50 consistent within ±15% |
Use molecular docking (HADDOCK, RosettaAntibody) guided by mutagenesis data (e.g., BEC2 paratope analysis [§0005])
Validate predictions with hydrogen-deuterium exchange mass spectrometry
Adopt a tiered validation system:
Cellular models: Primary human cells > immortalized lines (e.g., T98G vs. neuronal models in poly-GA studies )
Pharmacokinetics: Assess blood-brain barrier penetration (critical in neurological targets)
Species-specific validation: Test in ≥2 transgenic models (BAC vs. AAV models in C9orf72 research [Fig 3])