The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 19, 2025

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.

Language: Английский

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Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Nov. 3, 2022

Abstract Protein phosphorylation is an important post‐transcriptional modification involving extremely wide range of intracellular signaling transduction pathways, making it therapeutic target for disease intervention. At present, numerous drugs targeting protein have been developed the treatment various diseases including malignant tumors, neurological diseases, infectious and immune diseases. In this review article, we analyzed 303 small‐molecule kinase inhibitors (PKIs) registered participated in clinical research obtained a database named Kinase Inhibitor Database (PKIDB), 68 approved by Food Drug Administration United States. Based on previous classifications kinases, divided these human kinases into eight groups nearly 50 families, delineated their main regulatory upstream downstream targets. These include: A, G, C (AGC) receptor guanylate cyclase (RGC) group, calmodulin‐dependent (CaMK) CMGC [Cyclin‐dependent (CDKs), Mitogen‐activated (MAPKs), Glycogen synthase (GSKs), dc2‐like (CLKs)] sterile (STE)‐MAPKs tyrosine (TK) kinase‐like (TKL) atypical other groups. Different families stimulate or inhibit others, forming intricate molecular network. This takes newly new PKIs as breakthrough point, aiming to clarify network relationship each pathway, well roles intervention, provide direction future drug development.

Language: Английский

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The Microbiota–Gut–Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect

Nutrients, Journal Year: 2022, Volume and Issue: 14(10), P. 2081 - 2081

Published: May 16, 2022

Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which often accompanied by gastrointestinal symptoms. Experiments have demonstrated that disorder intestinal microbial system structure plays crucial role in depression. The gut-brain axis manifests potential linkage between digestion central nervous (CNS). Nowadays, it has become an emerging trend to treat diseases targeting microorganisms (e.g., probiotics) combining mechanism. Combined research, we found incidence depression closely linked gut microbiota. Moreover, transformation microbiota considered both positive negative regulatory effects on development This article reviewed mechanism bidirectional interaction existing symptom-relieving measures antidepression treatments related microbiome.

Language: Английский

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BDNF Therapeutic Mechanisms in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8417 - 8417

Published: July 29, 2022

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in adult brain and functions as both a primary signal neuromodulator. It serves essential roles neuronal development, maintenance, transmission, plasticity, thereby influencing aging, cognition, behavior. Accumulating evidence associates reduced central peripheral BDNF levels with various neuropsychiatric disorders, supporting its potential utilization biomarker of pathologies. Subsequently, extensive research has been conducted to evaluate restoring, or otherwise augmenting, transmission therapeutic approach. Promising results were indeed observed for genetic upregulation exogenous administration using multitude murine models neurological psychiatric diseases. However, varying mechanisms have proposed underlie effects, many findings indicate engagement disease-specific other non-specific mechanisms. This because essentially affects all aspects cellular function through tropomyosin receptor kinase B (TrkB) signaling, disruptions which vary between regions across different pathologies leading diversified consequences on cognition Herein, we review neurophysiology signaling classify converging diverging molecular underlying potentials disorders. These include neuroprotection, synaptic immunomodulation, plasticity facilitation, secondary neuromodulation, preservation neurovascular unit integrity viability. Lastly, discuss several suggesting common mediator actions centrally acting pharmacological agents used treatment illness.

Language: Английский

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Potential Role of Curcumin for the Treatment of Major Depressive Disorder

CNS Drugs, Journal Year: 2022, Volume and Issue: 36(2), P. 123 - 141

Published: Feb. 1, 2022

Curcumin is the major biologically active polyphenolic constituent in turmeric plant (Curcuma longa) that has been shown to have antioxidant, anti-inflammatory, neuroprotective, anticancer, antimicrobial, and cardioprotective effects. Interest curcumin as a treatment for mental health conditions increased there an expanding body of preclinical clinical research examining its antidepressant anxiolytic In this narrative review, human trials investigating effects depression or depressive symptoms are summarised. Using findings from vitro, animal, trials, possible biological mechanisms associated with also explored. To increase understanding depression, directions future proposed.

Language: Английский

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Biological Role of Nutrients, Food and Dietary Patterns in the Prevention and Clinical Management of Major Depressive Disorder

Nutrients, Journal Year: 2022, Volume and Issue: 14(15), P. 3099 - 3099

Published: July 28, 2022

Major Depressive Disorder (MDD) is a growing disabling condition affecting around 280 million people worldwide. This complex entity the result of interplay between biological, psychological, and sociocultural factors, compelling evidence suggests that MDD can be considered disease occurs as consequence an evolutionary mismatch unhealthy lifestyle habits. In this context, diet one core pillars health, influencing multiple biological processes in brain entire body. It seems there bidirectional relationship malnutrition, depressed individuals often lack certain critical nutrients along with aberrant dietary pattern. Thus, interventions are most promising tools to explore field MDD, specific group (i.e., omega 3, vitamins, polyphenols, caffeine), foods (fish, nuts, seeds fruits, vegetables, coffee/tea, fermented products) or supplements (such S-adenosylmethionine, acetyl carnitine, creatine, amino acids, etc.), which being currently studied. Likewise, nutritional context pattern seem another potential area study, some strategies such Mediterranean have demonstrated relevant benefits patients MDD; although, further efforts still needed. present work, we will state-of-the-art prevention clinical support focusing on properties its main nutrients, foods, patterns their possible implications for these patients.

Language: Английский

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The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer’s Disease as Highly Drug-Resistant Diseases: A Narrative Review

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(2), P. 163 - 163

Published: Jan. 18, 2023

Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is most widely distributed neurotrophin in central nervous system (CNS) and highly expressed prefrontal cortex (PFC) hippocampus. Its distribution outside CNS has also been demonstrated, but studies have focused its neuropsychiatric disorders. Despite advances medicine recent decades, neurological psychiatric diseases still characterized by high drug resistance. This review focuses use developmental assessment, treatment monitoring, pharmacotherapy selected diseases, a particular emphasis epilepsy, depression, anorexia, obesity, schizophrenia, Alzheimer's disease. The limitations using molecule such wide range inconsistent method determination highlighted.

Language: Английский

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Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 9, 2023

Intravenous ketamine is posited to rapidly reverse depression by enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 single infusion of intravenous (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments pre-infusion baseline 24-h post-infusion. DTI mean diffusivity (DTI-MD), putative marker matter, was calculated for 7 interest (left right BA10, amygdala, hippocampus; ventral Anterior Cingulate Cortex) compared clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) Quick Inventory Depressive Symptoms-Self-Report (QIDS-SR). Individual differences DTI-MD change (greater decrease from post-infusion, indicative more enhancement) associated larger improvements scores across several regions. left BA10 these relationships driven primarily group (group * interaction effects: p = 0.016-0.082). associations generalized both arms (p 0.007). hippocampus, MADRS only, effects observed opposite direction, such that inversely arm specifically 0.032-0.06). The acute may be mediated, part, quantifiable DTI.

Language: Английский

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How Oxidative Stress Induces Depression?

ASN NEURO, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

Depression increasingly affects a wide range and large number of people worldwide, both physically psychologically, which makes it social problem requiring prompt attention management. Accumulating clinical animal studies have provided us with substantial insights disease pathogenesis, especially central monoamine deficiency, considerably promotes antidepressant research treatment. The first-line antidepressants mainly target the system, whose drawbacks include slow action treatment resistant. novel esketamine, targeting on glutamatergic rapidly robustly alleviates depression (including treatment-resistant depression), efficiency is shadowed by potential addictive psychotomimetic side effects. Thus, exploring pathogenesis necessary, for seeking more safe effective therapeutic methods. Emerging evidence has revealed vital involvement oxidative stress (OS) in depression, inspires to pursue antioxidant pathway prevention Fully uncovering underlying mechanisms OS-induced first step towards avenue, thus we summarize expound possible downstream pathways OS, including mitochondrial impairment related ATP neuroinflammation, glutamate excitotoxicity, brain-derived neurotrophic factor/tyrosine receptor kinase B dysfunction serotonin microbiota-gut-brain axis disturbance hypothalamic-pituitary-adrenocortical dysregulation. We also elaborate intricate interactions between multiple aspects, molecular mediating interplay. Through reviewing progress field, hope depict an integral overview how OS induces order provide fresh ideas targets final goal efficient disease.

Language: Английский

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Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants

Chemical Reviews, Journal Year: 2023, Volume and Issue: 124(1), P. 124 - 163

Published: Nov. 30, 2023

Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated traditional psychedelic substances like psilocybin as class rapid-acting and long-lasting antidepressants. However, there is pressing need for rationally designed 5-HT2AR agonists possess optimal pharmacological profiles in order to fully reveal therapeutic potential these identify safer drug candidates devoid effects. This Perspective provides an overview structure–activity relationships existing based on their chemical classifications discusses recent advancements understanding molecular pharmacology at structural level. The encouraging clinical outcomes psychedelics depression treatment sparked discovery endeavors aimed developing novel with improved subtype selectivity signaling bias properties, which could serve potentially nonhallucinogenic These efforts can be significantly expedited through utilization structure-based methods functional selectivity-directed screening.

Language: Английский

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