Parthenolide changes ADORA2A coupling efficiency through membrane microdomain remodeling

ADORA2A neuropharmacology market 41% proposed
Composite
44%
Novelty
76%
Feasibility
50%
Impact
49%
Mechanistic
46%
Druggability
41%
Safety
46%
Confidence
38%

Mechanistic description

The scaffold alters receptor signaling efficacy without strong orthosteric affinity by modifying redox-sensitive lipid nanodomains.

Evidence for (6)

  • Coupling-specific assays could explain downstream selectivity without direct binding.

  • A(2A) Adenosine Receptor: A Possible Therapeutic Target for Alzheimer's Disease by Regulating NLRP3 Inflammasome Activity?

    PMID:35563447 2022 Int J Mol Sci

  • Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity.

    PMID:12711619 2003 Br J Pharmacol

  • Mitochondrial complex I as a therapeutic target for Alzheimer's disease.

    PMID:35256930 2022 Acta Pharm Sin B

  • Targeting the adenosine A(2A) receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease.

    PMID:37679245 2024 Chin J Traumatol

  • Caffeine for Prevention of Alzheimer's Disease: Is the A(2A) Adenosine Receptor Its Target?

    PMID:37371547 2023 Biomolecules

Evidence against (1)

  • This mechanism is currently underconstrained and easy to overfit post hoc.

Bayesian persona consensus

47% posterior support

1 signal · 0 for / 1 against · agreement 0%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.