ArticleFrontiers in pharmacology2020
The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Ketamine treatment alleviates suicide ideation in high-risk populations: a systematic review and meta-analysis.Epidemiology and psychiatric sciences · 2026Pooled it
- Research Progress and Future Perspectives of Orexin Receptor Antagonists in Insomnia Therapy.Molecules (Basel, Switzerland) · 2026Review
- Microglia-Dependent BDNF Signaling in the Dentate Gyrus Underlies the Antidepressant Effects of Gardiquimod, a Toll-Like Receptor 7 Agonist, in Chronically Stressed Mice.Neurochemical research · 2026Article
- Dentate Gyrus ERK1/2-BDNF Signaling is Required for the Antidepressant Effect of Microglial Stimulation in a Male Mouse Model of Depression Induced by Adolescent Nicotine Exposure.Neurochemical research · 2026Article
- A female-specific role for Slit1 in prenatal stress-induced depression vulnerability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- Duloxetine ameliorates chronic stress-induced depressive behaviors by normalizing hippocampal SIK2-CRTC1 signaling.Frontiers in pharmacology · 2026Article
- The multimodal antidepressant vortioxetine exerts therapeutic effects in male mice which is associated with normalization of hippocampal SIK2/CRTC1-related signaling and require hippocampal CRTC1.Frontiers in pharmacology · 2026Article
- SIK2-mediated phosphorylation of GABARAPL2 facilitates autophagosome-lysosome fusion and rescues neurodegeneration in an Alzheimer's disease model.Translational neurodegeneration · 2025Article
- Administration of chiglitazar reverses chronic stress-induced depressive-like symptoms in mice via activation of hippocampal PPARα and BDNF.Frontiers in pharmacology · 2025Article
- A novel probiotic formula, BLLL, ameliorates chronic stress-induced depression-like behaviors in mice by reducing neuroinflammation and increasing neurotrophic factors.Frontiers in pharmacology · 2024Article
- Blocking salt-inducible kinases with YKL-06-061 prevents PTZ-induced seizures in mice.Brain and behavior · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- The SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by microRNA-25-3p are altered in the schizophrenic rat brain.Frontiers in cellular neuroscience · 2023Article
- A protein-coding gene expression atlas from the brain of pregnant and non-pregnant goats.Frontiers in genetics · 2023Article
- Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods.Frontiers in pharmacology · 2023Article
- Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior.Molecular psychiatry · 2022Article
- Salt-inducible kinase 2 (SIK2) inhibitor ARN-3236 attenuates bleomycin-induced pulmonary fibrosis in mice.BMC pulmonary medicine · 2022Article
- New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity.Frontiers in molecular neuroscience · 2022Review
- Aminothioneine, a product derived from golden oyster mushrooms (Biochemistry and biophysics reports · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible kinase 2 (SIK2). In this study, a multidisciplinary approach was used to explore the antidepressant-like actions of ARN-3236 in mice. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. It was found that ARN-3236 could penetrate the blood-brain barrier. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Moreover, we demonstrated that the hippocampal CRTC1-CREB-BDNF pathway mediated the antidepressant-like efficacy of ARN-3236. Collectively, ARN-3236 possesses strong protecting effects against chronic stress, and could be a novel antidepressant beyond monoaminergic drugs.
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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 OpenQuestion graph.