ReviewMolecular biology reports2025
Rap1-Dependent pathways in depression: Genetic, Epigenetic, and neuroinflammatory mechanisms shaping synaptic resilience.
Review in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- A de novo Loss-of-function Variant in RAPGEF6 Supports its Role in Neuropsychiatric Disorders.Journal of molecular neuroscience : MN · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rap1, a small GTPase integral to synaptic plasticity, has emerged as a pivotal regulator in the pathophysiology of depression, bridging molecular, genetic, and environmental mechanisms. This review synthesizes evidence highlighting Rap1's role in long-term depression (LTD) and dendritic spine remodeling, where isoform-specific interactions (Rap1 vs. Rap2) modulate AMPA receptor trafficking and synaptic resilience. Genetic studies implicate Rap1-associated pathways, such as DOCK2 and DIRAS2, in postpartum depression, while postmortem analyses reveal reduced Rap1 activity in mood-related brain regions of depressed individuals. Epigenetic regulation, particularly stress-induced FTO downregulation, disrupts Rap1-dependent synaptic protein translation, linking environmental stressors to maladaptive plasticity. Neuroimmune crosstalk further underscores Rap1's dual role in synaptic and inflammatory signaling, as seen in comorbid depression and atopic dermatitis. Environmental toxins like cadmium dysregulate Rap1 via oxidative stress and epigenetic modifications, while phytocannabinoids modulate Rap1-ERK pathways to enhance neuroprotection. Therapeutic strategies, including vortioxetine and natural compounds like Modified Xiaoyaosan, target Rap1 to restore synaptic homeostasis. Emerging pathways, such as circadian disruptions and gut-brain axis interactions, suggest novel mechanisms by which Rap1 integrates systemic and neuronal stress responses. Unresolved questions persist regarding Rap1 isoform specificity, spatiotemporal regulation, and glial-neuronal metabolic coupling, necessitating advanced tools like biosensors and organoid models to unravel its pleiotropic roles in depression.
Indexed as
Identifiers
41369997What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.