NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer’s Disease

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2587 - 2587

Published: Sept. 21, 2023

The nuclear factor kappa B (NF-κB) pathway has emerged as a pivotal player in the pathogenesis of various diseases, including neurodegenerative illnesses like Alzheimer’s disease (AD). involvement NF-κB immune system responses, inflammation, oxidative stress, and neuronal survival highlights its significance AD progression. We discuss advantages inhibition, potential to mitigate neuroinflammation, modulate amyloid beta (Aβ) production, promote survival. However, we also acknowledge limitations challenges associated with this approach. Balancing fine line between dampening inflammation preserving physiological responses is critical avoid unintended consequences. This review combines current knowledge on pathway’s intricate pathogenesis, emphasizing therapeutic target. By evaluating both limitations, provide holistic view feasibility modulation treatment. As quest for effective therapies continues, an in-depth understanding multifaceted roles will guide development targeted interventions improve management.

Language: Английский

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The growing range of complications of diabetes mellitus

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Investigation of Thiazolidine‐2,4‐Dione Derivatives as Acetylcholinesterase Inhibitors: Synthesis, In Vitro Biological Activities and In Silico Studies

ChemistryOpen, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

The inhibition of acetylcholinesterase (AChE), an enzyme responsible for the inactivation and decrease in acetylcholine cholinergic pathway, has been considered attractive target small-molecule drug discovery Alzheimer's disease (AD) therapy. In present study, a series TZD derivatives were designed, synthesized, studied likeness, blood-brain barrier (BBB) permeability, adsorption, distribution, metabolism, excretion, toxicity (ADMET). Additionally, docking studies designed compounds performed on AChE. all (CHT1-5) showed acceptable affinity AChE inhibition, results convincing binding modes active site Among them, 5-(4-methoxybenzylidene) thiazolidine-2,4-dione (CHT1) was identified as most potent inhibitor (IC

Language: Английский

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Insulin resistance as the molecular link between diabetes and Alzheimer's disease

World Journal of Diabetes, Journal Year: 2024, Volume and Issue: 15(7), P. 1430 - 1447

Published: July 8, 2024

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.

Language: Английский

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Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

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Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12488 - 12488

Published: Aug. 6, 2023

Mitochondria, far beyond their prominent role as cellular powerhouses, are complex organelles active central metabolic hubs that capable of integrating and controlling several signaling pathways essential for neurological processes, including neurogenesis neuroplasticity. On the other hand, mitochondria themselves regulated from a series proteins to achieve best efficiency in producing energy, establishing network performing own de novo synthesis or clearance. Dysfunctions processes control mitochondrial biogenesis, dynamics bioenergetics increasingly associated with impairment brain development involved wide variety neurodevelopmental disorders. Here, we review recent evidence proving emerging master regulators bioenergetics, highlighting skills neurodevelopment cognition. We analyze, mechanistic point view, bioenergetic dysfunction causally interrelated origins typical genetic intellectual disability-related disorders, such Down, Rett Fragile X syndromes. Finally, discuss whether can become therapeutic targets improve function holistic perspective.

Language: Английский

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Dopamine in the Regulation of Glucose Homeostasis, Pathogenesis of Type 2 Diabetes, and Chronic Conditions of Impaired Dopamine Activity/Metabolism: Implication for Pathophysiological and Therapeutic Purposes

Biomedicines, Journal Year: 2023, Volume and Issue: 11(11), P. 2993 - 2993

Published: Nov. 7, 2023

Dopamine regulates several functions, such as voluntary movements, spatial memory, motivation, sleep, arousal, feeding, immune function, maternal behaviors, and lactation. Less clear is the role of dopamine in pathophysiology type 2 diabetes mellitus (T2D) chronic complications conditions frequently associated with it. This review summarizes recent evidence on regulating insular metabolism activity, traditional T2D, pathophysiological interconnection between T2D neurological psychiatric disorders characterized by impaired activity/metabolism, therapeutic implications. Reinforcing signaling especially patients dopamine-related disorders, Parkinson’s Huntington’s diseases, addictions, attention-deficit/hyperactivity disorder. On other hand, although specific trials are probably needed, certain medications approved for (e.g., metformin, pioglitazone, incretin-based therapy, gliflozins) may have a due to anti-inflammatory anti-oxidative effects, improvement insulin signaling, neuroinflammation, mitochondrial dysfunction, autophagy, apoptosis, restoration striatal synthesis, modulation reward hedonic eating. Last, targeting could potential diagnostic purposes diabetes-related complications, diabetic retinopathy.

Language: Английский

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Therapeutic Potential and Challenges of Pioglitazone in Cancer Treatment

Applied Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 1925 - 1925

Published: Feb. 13, 2025

Pioglitazone (ACTOS) is a thiazolidinedione for peroxisome proliferator-activated receptor γ (PPAR-γ) that has been well established the second or third line treatment of type 2 diabetes mellitus. Beyond effects on glucose metabolism, pioglitazone displays positive lipid blood pressure, endothelial function, bone density, and apoptosis cancer cells. In fact, according to in vitro experiments preclinical studies, PPAR-γ ligand currently considered potential target both chemoprevention therapy. ligands are known inhibit cell proliferation metastasis through terminal differentiation underexpression inflammatory mediators. Despite its anticancer properties, was withdrawn by national medicine agencies France Germany, due reports increased incidence bladder cancer. These were associated with European populations undergoing higher doses longer durations treatment. this review, we discuss pharmacokinetics, therapeutic potential, limitations regarding clinical use pioglitazone, focus

Language: Английский

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Pioglitazone improves learning and memory in a rat model of cholinergic dysfunction induced by scopolamine, the roles of oxidative stress and neuroinflammation

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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The double-edged sword of nutraceuticals: comprehensive review of protective agents and their hidden risks

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: March 27, 2025

Nutraceuticals-including resveratrol (RSV), curcumin (CUR), piperine (PPR), and quercetin (QUE)-exhibit dual therapeutic toxicological profiles, are necessitating balanced risk–benefit evaluation. This review synthesizes evidence from about 120 preclinical/clinical studies sourced PubMed, Scopus, Web of Science using keywords (e.g., nutraceutical-drug interactions, bioavailability, CYP/P-gp modulation), prioritizing recent advances (2015–2024) alongside seminal works to contextualize mechanisms. Studies were selected based on methodological rigor, clinical relevance, mechanistic insights into protective effects (antioxidant, anti-inflammatory, anticancer) risks (organ toxicity, pro-oxidant activity, drug interactions). Key findings highlight PPR’s bioavailability-enhancing neuroprotective properties, yet its inhibition CYP3A4/P-gp elevates toxicity for carbamazepine (68.7% ↑ plasma concentration) warfarin. CUR demonstrates hepatoprotective benefits but alters cardiovascular pharmacokinetics amlodipine) induces oxidative stress at high doses. RSV QUE improve cardiovascular/neurological outcomes interact with chemotherapeutics (RSV ↓ resistance via apoptosis; methotrexate efficacy anti-inflammatory synergy). Critical include reproductive (PPR >10 mg/kg), neurocognitive deficits (high-dose CUR), CYP3A4-mediated interactions (QUE + cyclosporine). Nanotechnology-driven formulations CUR/PPR nanoemulsions) mitigate by enhancing stability enabling targeted delivery, though rigorous safety validation remains essential. underscores the need evidence-based guidelines optimize nutraceutical use in polypharmacy populations, emphasizing interdisciplinary collaboration manage interactions. Innovations like nanoencapsulation could transition nutraceuticals supplements precision medicine adjuvants, pending resolution dose–response ambiguities long-term gaps through research.

Language: Английский

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