Apoptosis in Alzheimer’s disease: insight into the signaling pathways and therapeutic avenues

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(7-8), P. 943 - 957

Published: April 26, 2023

Language: Английский

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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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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Language: Английский

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JAK2/STAT3 as a new potential target to manage neurodegenerative diseases: An interactive review

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 970, P. 176490 - 176490

Published: March 15, 2024

Language: Английский

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Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer’s disease mouse model

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110783 - 110783

Published: Aug. 22, 2023

Language: Английский

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Genkwanin: An emerging natural compound with multifaceted pharmacological effects

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115159 - 115159

Published: July 21, 2023

Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress low-grade inflammation. Dietary antioxidants, including genkwanin, decrease expression pro-inflammatory cytokines or pathways. The present study is first comprehensive review a methoxyflavone found several plant species. Indeed, natural sources, pharmacokinetics biological properties were discussed highlighted detail. This analyzed considered all original studies related to identification, isolation, quantification, investigation pharmacological genkwanin. We consulted published papers peer-reviewed journals English language from inception each database 12 May 2023. Different phytochemical demonstrated that genkwanin non-glycosylated flavone isolated medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia Leonurus sibiricus. In vitro vivo investigations showed Genkwanin exhibits remarkable antioxidant anti-inflammatory activities, via activation glucokinase, has shown antihyperglycemic activity with potential role against metabolic syndrome diabetes. Additionally, it revealed cardioprotective neuroprotective properties, thus reducing risk cardiovascular diseases assisting neurodegenerative diseases. Furthermore, other like antitumor capability, antibacterial, antiviral, dermato-protective effects. involved mechanisms include sub-cellular, cellular molecular actions at different levels inducing apoptosis inhibiting growth proliferation cancer cells. Despite findings preclinical have effects its diverse action, additional research required comprehensively explore potential. Primarily, extensive should be carried out enhance our understanding molecule's pharmacodynamic pharmacokinetic Moreover, toxicological clinical undertaken assess safety efficacy These forthcoming are utmost importance fully unlocking this molecule realm applications.

Language: Английский

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Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 200 - 200

Published: Feb. 7, 2024

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, condition a high occurrence rate ranks second in terms mortality. The development new drugs been facilitated by increased research deeper understanding mechanisms behind emergence advancement disease. Numerous preclinical clinical studies have repeatedly demonstrated protective effects natural terpenoids against range malignancies. potential bioactive investigated sources for their chemopreventive chemoprotective properties. In practically all body cells, signaling molecule referred to as signal transducer activator transcription 3 (STAT3) is widely expressed. that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, survivin, promote growth differentiation, cell cycle progression, angiogenesis, immune suppression addition chemotherapy resistance. Researchers viewed primary cancer therapy because crucial involvement formation. This primarily focuses on directly indirectly preventing expression tumor cells. By explicitly targeting both vitro vivo settings, it possible explain effect malignant this study, we provide complete overview transduction processes, carcinogenesis, related persistent activation. article also thoroughly summarizes inhibition certain terpenoid phytochemicals, which strong efficacy several models.

Language: Английский

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A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract β‐secretase (BACE1) is instrumental in amyloid‐β (Aβ) production, with overexpression noted Alzheimer's disease (AD) neuropathology. The interaction of Aβ the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake and exacerbates its neurotoxicity neuroinflammation, further augmenting BACE1 expression. Given limitations previous inhibition efforts, study explores reducing expression to mitigate AD pathology. research reveals that anticancer agent 6‐thioguanosine (6‐TG) markedly diminishes without eliciting cytotoxicity while enhancing microglial phagocytic activity, ameliorate cognitive impairments accumulation mice. Leveraging deep learning‐based tool target identification, corroborating surface plasmon resonance assays, it elucidated 6‐TG directly interacts RAGE, modulating through JAK2‐STAT1 pathway elevating soluble RAGE (sRAGE) levels brain. findings illuminate therapeutic potential ameliorating manifestations advocate small molecule strategies increase brain sRAGE levels, offering a strategic alternative challenges posed by complexity AD.

Language: Английский

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Exploring the mechanism of Radix Bupleuri in the treatment of depression combined with SARS-CoV-2 infection through bioinformatics, network pharmacology, molecular docking, and molecular dynamic simulation

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 17, 2025

Language: Английский

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Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 133 - 133

Published: Jan. 20, 2025

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by dysregulation molecular pathways and activation brain’s immune system, resulting release pro-inflammatory oxidative molecules. This chronic inflammation exacerbated peripheral leukocyte infiltration into central nervous system. Medicinal plants, with their historical use traditional medicine, have emerged as promising candidates to mitigate neuroinflammation offer sustainable alternative for addressing conditions green healthcare framework. review evaluates effects medicinal plants on neuroinflammation, emphasizing mechanisms action, effective dosages, clinical implications, based systematic search databases such PubMed, SCOPUS, Web Science. The findings highlight that like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, Dioscorea nipponica reduce cytokines (TNF-α, IL-6, IL-1β), inhibit enzymes (COX-2 iNOS), activate antioxidant pathways, particularly Nrf2. NF-κB primary pathway inhibited across studies. While anti-inflammatory potential these significant, variability dosages phytochemical compositions limits translation. Here, we are modulators underscoring therapeutic potential. Future research should focus animal models, standardized protocols, safety assessments, integrating advanced methodologies, genetic studies nanotechnology, enhance applicability disease management.

Language: Английский

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