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G Protein–Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders

2025· review· en· W4406811653 on OpenAlexaff
Ahmed Hasbi, Susan R. George

Bibliographic record

VenueThe Annual Review of Pharmacology and Toxicology · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsG protein-coupled receptorContext (archaeology)ReceptorNeuroscienceComputational biologyDrug discoveryDrug developmentFunction (biology)BiologyFunctional selectivityDrugChemistryBioinformaticsPharmacologyCell biologyBiochemistry

Abstract

fetched live from OpenAlex

G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers. Greater acceptance of oligomerization occurred with the recognition that GPCR interactions form heteromeric receptor complexes, which was validated in vivo, often with pharmacologic, signaling, and functional properties distinct from the constituent protomers. GPCR heteromerization is reviewed in the context of brain disorders, with examples illustrating their functional implication in diverse neuropsychiatric and neurodegenerative disorders, making them an enormous unexploited resource for selective pharmacotherapy target identification. The strategies for development of heteromer-selective ligands are discussed as a new opportunity to precisely target the function of a receptor complex with greater specificity, in contrast to the classical ligands targeting individual receptors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.986
Threshold uncertainty score0.983

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.317
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations13
Published2025
Admission routes1
Has abstractyes

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