JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Nov. 8, 2023

Abstract The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological pathological processes such inflammation stress. Dysregulation this can lead to severe immunodeficiencies malignancies, its role extends neurotransduction pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological inflammatory disorders, their application has generally been limited diseases with similar pathogenic features. Despite the modest expression of JAK-STAT CNS, it is crucial for functions cortex, hippocampus, cerebellum, making relevant conditions like Parkinson's disease other neuroinflammatory disorders. Furthermore, influence on serotonin receptors phospholipase C implications stress mood This review expands understanding JAK-STAT, moving beyond traditional contexts explore stress-related disorders CNS function. Recent findings, effectiveness Jakinibs chronic rheumatoid arthritis, expand therapeutic applicability. Advances isoform-specific inhibitors, including filgotinib upadacitinib, promise greater specificity fewer off-target effects. Combination therapies, involving monoclonal antibodies, aiming enhance efficacy also give great hope. Overall, bridges gap between basic science clinical application, elucidating complex human health guiding future interventions. Graphical

Language: Английский

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Neurobiology and systems biology of stress resilience

Physiological Reviews, Journal Year: 2024, Volume and Issue: 104(3), P. 1205 - 1263

Published: March 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Language: Английский

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Functional resting state connectivity is differentially associated with IL-6 and TNF-α in depression and in healthy controls

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 13, 2025

Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has shown to act as a critical disease modifier, promoting susceptibility depression and modulating specific endophenotypes However, there is scant documentation how inflammatory are associated with neural activity patients We therefore tested hypothesis that peripheral markers IL-6 TNF-α correlate resting state network functional connectivity using magnetic resonance imaging (fMRI) compared it healthy controls. used fMRI investigate (FC) Default Mode Network (DMN) Salience/Ventral Attention (SAL) their association 25 24 subjects. Results this study revealed both DMN SAL networks differentially distinct immunological pathways depending on whether person depressive phenotype or healthy. While FC correlated concentration cytokine subjects, FC's TNF-α's concentration. This highlights importance suggests modulatory effect

Language: Английский

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The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108825 - 108825

Published: Feb. 1, 2025

Language: Английский

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Associations between metabolic syndrome and anxiety, and the mediating role of inflammation: Findings from the UK Biobank

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 116, P. 1 - 9

Published: Nov. 19, 2023

Language: Английский

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Pro-inflammatory cytokines in stress-induced depression: Novel insights into mechanisms and promising therapeutic strategies

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 131, P. 110931 - 110931

Published: Jan. 2, 2024

Language: Английский

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Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3203 - 3203

Published: March 11, 2024

Mental disorders account for one of the most prevalent categories burden disease worldwide, with depression expected to be largest contributor by 2030, closely followed anxiety. The COVID-19 pandemic possibly exacerbated these challenges, especially amongst adolescents, who experienced isolation, disrupted routines, and limited healthcare access. Notably, has been associated long-term neurological effects known as “long-COVID”, characterized both cognitive psychopathological symptoms. In general, psychiatric disorders, including those related long-COVID, are supposed due widespread inflammation leading neuroinflammation. Recently, endocannabinoid system (ECS) emerged a potential target addressing anxiety pathophysiology. Specifically, natural or synthetic cannabinoids, able selectively interact cannabinoid type-2 receptor (CB2R), recently revealed new therapeutic in neuropsychiatric absent psychotropic activity. Among promising CB2R ligands, bicyclic sesquiterpene β-caryophyllene (BCP) an excellent anti-inflammatory antioxidant agent. This review underscores BCP’s immunomodulatory properties, highlighting its management

Language: Английский

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Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 26, 2024

Abstract The question of whether immune dysfunction contributes to risk psychiatric disorders has long been a subject interest. To assert this hypothesis plethora correlative evidence accumulated from the past decades; however, variety technical and practical obstacles impeded on cause-effect interpretation these data. With advent large-scale omics technology advanced statistical models, particularly Mendelian randomization, new studies testing old are accruing. Here we synthesize findings genomics genetic causal inference role in major reconcile data with pre-omics findings. By reconciling evidences, aim identify key gaps propose directions for future field.

Language: Английский

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Glucagon‐like peptide agonists for weight management in antipsychotic‐induced weight gain: A systematic review and meta‐analysis

Acta Psychiatrica Scandinavica, Journal Year: 2024, Volume and Issue: 150(6), P. 516 - 529

Published: July 24, 2024

Managing body weight in patients with antipsychotic-induced gain (AIWG) is challenging. Besides lifestyle interventions, pharmacological interventions may contribute to loss. This systematic review and meta-analysis evaluated the effect on loss adverse effects of glucagon-like peptide-1 (GLP-1) agonists AIWG.

Language: Английский

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Neurotrophin-3 as a mediator in the link between PM2.5 exposure and psychiatric disorders: A Mendelian randomization study

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 289, P. 117658 - 117658

Published: Jan. 1, 2025

The causal relationship between PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm) and common mental disorders, along its neuropathological mechanisms, remains unclear. We used genome-wide association study datasets from the UK Biobank Psychiatric Genomics Consortium to systematically investigate nine psychiatric disorders using two-sample Mendelian randomization (TSMR) methods. Subsequently, we two-step MR mediating effect of 108 potential mediators in disorders. Our findings indicated that was positively associated major depressive disorder (odds ratio (OR): 1.33, 95 % confidence interval (CI): 1.11-1.55), anxiety (OR: 2.96, CI: 2.13-3.79), schizophrenia 1.55, 1.29-1.81), attention deficit hyperactivity (ADHD) 1.95, 1.66-2.24). Unexpectedly, inversely bipolar 0.65, 0.37-0.93). Additionally, not significantly autism spectrum 1.24, 0.83-1.65), post-traumatic stress 1.51, 1.11-1.91), obsessive-compulsive 0.81, -0.07-1.69), or anorexia nervosa 1.42, 0.86-1.98). Further analysis revealed Neurotrophin-3 mediated 9.86 PM2.5-ADHD 5.88 PM2.5-schizophrenia association. Sensitivity analyses supported these findings. This TSMR provides a comprehensive examination exposure mediation offering insight into underlying mechanisms. aims raise public awareness how air quality affects health through empirical evidence.

Language: Английский

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