Are FXR Family Proteins Integrators of Dopamine Signaling and Glutamatergic Neurotransmission in Mental Illnesses?
Bibliographic record
Abstract
Dopamine receptors and related signaling pathways have long been implicated in pathophysiology and treatment of mental disorders. Dopamine signaling may impact neuronal activity by modulation of glutamate neurotransmission. Recent evidence indicates a direct and/or indirect involvement of fragile X related family proteins (FXR) in the regulation and mediation of dopamine receptor functions. FXRs consists of fragile X mental retardation protein 1 (Fmr1/FMRP) and its autosomal homologs Fxr1 and Fxr2. These RNA-binding proteins are enriched in the brain. Loss of function mutation in human FMR1 is the major genetic contributor to Fragile X mental retardation syndrome. Therefore, the role of FXR proteins has mostly been studied in the context of autism spectrum disorders. However, recent genome-wide association studies have linked this family to schizophrenia, bipolar disorders and mood regulation pointing toward a broader involvement in mental illnesses. FXR family proteins play an important role in the regulation of glutamate-mediated neuronal activity and plasticity. Here, we discuss the brain-specific functions of FXR family proteins by focusing on regulation of dopamine receptor functions, ionotropic glutamate receptors mediated synaptic plasticity and contribution to mental illnesses. Based on the recent evidence we propose that FXR proteins are potential integrators of dopamine signaling and ionotropic glutamate transmission.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".