Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: July 26, 2022

Abstract The Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway is involved in many immunological processes, including cell growth, proliferation, differentiation, apoptosis, inflammatory responses. Some these processes can contribute to cancer progression neurodegeneration. Owing the complexity this its potential crosstalk with alternative pathways, monotherapy as targeted therapy has usually limited long-term efficacy. Currently, majority JAK–STAT-targeting drugs are still at preclinical stages. Meanwhile, a variety plant polyphenols, especially quercetin, exert their inhibitory effects on JAK–STAT through known unknown mechanisms. Quercetin shown prominent terms anti-inflammatory antitumor activity, well control neurodegenerative diseases. This review discusses pharmacological quercetin signaling solid tumors

Language: Английский

---

PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: April 18, 2023

Abstract Microglia are the immune effector cells of brain playing critical roles in surveillance and neuroprotection healthy conditions, while they can sustain neuroinflammatory neurotoxic processes neurodegenerative diseases, including Parkinson’s disease (PD). Although precise triggers PD remain obscure, causative genetic mutations, which aid identification molecular pathways underlying pathogenesis idiopathic forms, represent 10% patients. Among inherited loss function PARK7 , encodes protein DJ-1, results autosomal recessive early-onset PD. Yet, although protection against oxidative stress is most prominent task ascribed to mechanisms linking DJ-1 deficiency onset a current matter investigation. This review provides an overview role neuroinflammation, with special focus on its functions microglia programs immunological traits. Furthermore, it discusses relevance targeting dysregulated under their importance as therapeutic targets Lastly, addresses prospect consider detected oxidized form PD, biomarker take into account DJ-1-enhancing compounds therapeutics dampening neuroinflammation.

Language: Английский

---

Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review

Molecules, Journal Year: 2024, Volume and Issue: 29(4), P. 866 - 866

Published: Feb. 15, 2024

Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They found many traditional medicinal systems play key role restoring body’s strength stamina. Research recent years has attempted elucidate mechanisms behind their pharmacological effects, but it appears these difficult define precisely involve multiple molecular pathways. Neuroinflammation: In years, chronic inflammation been recognized as one common features central nervous system disorders (dementia other neurodegenerative diseases, depression, anxiety, ischemic stroke, infections). Because specific nature brain, this process is called neuroinflammation, suppression can result an improvement patients’ condition may promote recovery. anti-inflammatory agents: As discovered, adaptogens display which suggests application be broader than previously thought. regulate gene expression anti- proinflammatory cytokines (prostaglandins, leukotriens) modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims present anti-neuroinflammatory potential most important classified adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea Withania somnifera.

Language: Английский

---

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome

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

Published: Jan. 18, 2024

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely adults. Inflammation is characteristic of some, not all, patients with ADHD might be influenced by medication also lifestyle factors including nutrition, smoking, stress. It still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins a deeply phenotyped cohort 126 adult participants stable status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the based on their profile: higher potential (HIP) lower protein (LIP) group. Biological processes that differed strongest groups were NF-κB pathway, chemokine signaling, IL-17 metabolic alterations, attraction. comparison sample characteristics revealed HIP group was more likely have levels chronic stress (p < 0.001), clinical global impression scale score = 0.030), risk for suicide 0.032). Medication did influence significantly ≥ 0.074), psychotropic co-medication ≤ 0.009) did. In conclusion, our data suggest presence adults ADHD. Higher linked perceived linear fashion. Further research should take into account.

Language: Английский

---

Gut-brain axis interplay via STAT3 pathway: Implications of Helicobacter pylori derived secretome on inflammation and Alzheimer’s disease

Virulence, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 10, 2024

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides complications its potential link with gut-brain axis disruption neurological disorders has also been reported. The current study investigated the plausible role associated molecular mechanism underlaying H. mediated neuroinflammation leading to modalities like Alzheimer's disease (AD). We have chosen antimicrobial resistant susceptible strains on basis of broth dilution method. observed increased inflammatory response exerted by in as well neuronal compartment after treatment derived condition media (HPCM). Further, elevated expression STAT1, STAT3, AD-associated proteins- APP APOE4 was monitored HPCM-treated neuron-astrocyte co-cultured cells. Excessive ROS generation found these HPCM LN229 astrogliosis, evidenced glial fibrillary acidic protein. Our results indicate association STAT3 an important regulator pylori-mediated pathogenesis Notably, inhibition specific inhibitor, BP-1-102, reduced pSTAT3 AD markers induced HPCM. Thus, our demonstrates infection exacerbates inflammation AGS cells modulates activity regulatory molecules. secretome could affect compartments promoting activation inducing signature markers. pSTAT-3 mitigates amyloid pathology.

Language: Английский

---

Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer’s Disease

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 168 - 168

Published: Jan. 22, 2025

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression

Language: Английский

---

Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's and Huntington's are complex challenging due to their intricate pathophysiology limited treatment options. This review systematically sourced articles related neurodegenerative diseases, neurodegeneration, quercetin, clinical studies from primary medical databases, Scopus, PubMed, Web of Science. Recent have included quercetin impact the cellular molecular pathways involved in neurodegeneration. Quercetin, a flavonoid abundant vegetables fruits, is gaining attention for its antioxidant, anti-inflammatory, antiapoptotic properties. It regulates signaling such as nuclear factor-κB (NF-κB), sirtuins, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). These essential survival, inflammation regulation, apoptosis. Preclinical shown that improves symptoms pathology models, indicating promising outcomes. The study explores potential incorporating laboratory research into practical treatment, focusing on quercetin's neuroprotective effects NDs optimal dosage.

Language: Английский

---

Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 394 - 394

Published: March 11, 2025

Background: Janus kinase (JAK) inhibitors are a new class of targeted therapies that block cytokines and the signal transduction activators transcription (STAT) pathway. However, post-marketing surveillance studies have led to revised recommendations, highlighting potential serious heart-related events cancer risk JAK inhibitors. Here, we aimed determine neurological adverse (AEs) (tofacitinib, ruxolitinib, baricitinib) based on global real-world database. Methods: We analyzed individual case safety reports from Uppsala Monitoring Center January 1968 4 April 2022. A disproportionality analysis was performed using proportional reporting ratio (PRR), odds (ROR), information component (IC) detect signals. Signals were classified according hierarchy Medical Dictionary for Regulatory Activities (MedDRA). Additionally, stratified by age group sex major AEs. Results: total 30,051,159 all drugs in this study. Among 105,798 tofacitinib, 14.1% (14,863 reports) For ruxolitinib baricitinib, 14.5% (6317 10.2% (1216 AEs, respectively. Various AE signals detected tofacitinib with memory impairment exhibiting highest number positive group. Baricitinib did not reach detection threshold. Conclusions: This study suggests including impairment, associated use

Language: Английский

---

EPO prevents neuroinflammation and relieves depression via JAK/STAT signaling

Life Sciences, Journal Year: 2023, Volume and Issue: 333, P. 122102 - 122102

Published: Sept. 26, 2023

Language: Английский

---

Anti-Neuroinflammatory Potential of Natural Products in the Treatment of Alzheimer’s Disease

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1486 - 1486

Published: Feb. 3, 2023

Alzheimer’s disease (AD) is an age-related chronic progressive neurodegenerative disease, which the main cause of dementia in elderly. Much evidence shows that onset and late symptoms AD are caused by multiple factors. Among them, aging factor pathogenesis AD, most important risk for neuroinflammation. So far, there no cure but relationship between neuroinflammation may provide a new strategy treatment AD. We herein discussed etiology hypothesis role as well anti-inflammatory natural products with potential to prevent alleviate symptoms, including alkaloids, steroids, terpenoids, flavonoids polyphenols, available great development anti-AD drugs.

Language: Английский

---