ArticleMolecular psychiatry2022
Inhibition of FKBP51 induces stress resilience and alters hippocampal neurogenesis.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Standardized chronic restraint stress protocols reveal dynamic evolution of behavioral adaptations in male mice: implications for translational neuroscience.Molecular psychiatry · 2026Article
- Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia.Science advances · 2026Article
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- TGR5 is essential for protecting from chronic stress-induced learning and memory impairments in mice by modulating inflammation associated with the gut-brain axis.Journal of neuroinflammation · 2026Article
- Inhibition of FKBP51 alleviates depressive-like behaviors via AKT/mTOR-dependent autophagy and synaptic plasticity.The international journal of neuropsychopharmacology · 2026Article
- The synaptic triad in depression: how stress-related pathways converge on BDNF, NMDA receptor, and MMP-9.Pharmacological reports : PR · 2026Review
- Epigenetic Basis of Stress-Induced Central Nervous System Disorders: Therapeutic Approaches.Biology · 2026Review
- Unraveling Complex Interactions Mechanisms Linking PTSD and Chronic Diseases.Current neuropharmacology · 2026Review
- Analgesia through FKBP51 inhibition at disease onset confers lasting relief from sensory and emotional chronic pain symptoms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- FKBP5 Induces Senescence in BMSCs and Inhibits Osteogenic Differentiation Through the Canonical WNT/β-Catenin Signalling Pathway in Senile Osteoporosis.Journal of cellular and molecular medicine · 2025Article
- Association Between Stress-Induced Weight Loss and Autophagy-Related Gene Expression in the Hippocampus and Midbrain of Depression Model Mice.Neuropsychopharmacology reports · 2025Article
- Central nervous system and immune cells interactions in cancer: unveiling new therapeutic avenues.Frontiers in immunology · 2025Review
- Photobiomodulation: shining a light on depression.Theranostics · 2025Review
- In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders.PloS one · 2025Article
- Corticosterone effects induced by stress and immunity and inflammation: mechanisms of communication.Frontiers in endocrinology · 2025Review
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- Reducing FKBP51 Expression in the Ventral Hippocampus Decreases Auditory Fear Conditioning in Male Rats.International journal of molecular sciences · 2024Article
- The Role of FKBPs in Complex Disorders: Neuropsychiatric Diseases, Cancer, and Type 2 Diabetes Mellitus.Cells · 2024Review
- DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans.Molecular psychiatry · 2024Article
- The missing hallmark of health: psychosocial adaptation.Cell stress · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress-related psychiatric disorders such as depression are among the leading causes of morbidity and mortality. Considering that many individuals fail to respond to currently available antidepressant drugs, there is a need for antidepressants with novel mechanisms. Polymorphisms in the gene encoding FK506-binding protein 51 (FKBP51), a co-chaperone of the glucocorticoid receptor, have been linked to susceptibility to stress-related psychiatric disorders. Whether this protein can be targeted for their treatment remains largely unexplored. The aim of this work was to investigate whether inhibition of FKBP51 with SAFit2, a novel selective inhibitor, promotes hippocampal neuron outgrowth and neurogenesis in vitro and stress resilience in vivo in a mouse model of chronic psychosocial stress. Primary hippocampal neuronal cultures or hippocampal neural progenitor cells (NPCs) were treated with SAFit2 and neuronal differentiation and cell proliferation were analyzed. Male C57BL/6 mice were administered SAFit2 while concurrently undergoing a chronic stress paradigm comprising of intermittent social defeat and overcrowding, and anxiety and depressive -related behaviors were evaluated. SAFit2 increased neurite outgrowth and number of branch points to a greater extent than brain derived neurotrophic factor (BDNF) in primary hippocampal neuronal cultures. SAFit2 increased hippocampal NPC neurogenesis and increased neurite complexity and length of these differentiated neurons. In vivo, chronic SAFit2 administration prevented stress-induced social avoidance, decreased anxiety in the novelty-induced hypophagia test, and prevented stress-induced anxiety in the open field but did not alter adult hippocampal neurogenesis in stressed animals. These data warrant further exploration of inhibition of FKBP51 as a strategy to treat stress-related disorders.
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