Molecular Mechanisms of Neuroprotection: The Interplay of Klotho, SIRT-1, Nrf2, and HO-1 in Neurological Health DOI

R.S. Rana,

R Mukherjee,

Sidharth Mehan

et al.

Behavioural Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 115545 - 115545

Published: March 1, 2025

Language: Английский

Neuroinflammation in Alzheimer’s Disease DOI Creative Commons
Isaac G. Onyango, Gretsen Velezmoro Jáuregui, Mária Čarná

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 524 - 524

Published: May 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Language: Английский

Citations

209

Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway DOI Creative Commons
Ruijin Xie,

Wenjing Zhao,

Scott Lowe

et al.

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 191, P. 212 - 226

Published: Sept. 7, 2022

Epilepsy is one of the most common neurological disorders in childhood. However, classical antiepileptic drugs are linked with drug toxicity and cognitive function impairment children. Hence, it essential to develop a novel therapy solve this problem. Currently, studies indicate regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated ferroptosis pathway represents potential advanced for seizures. present study aimed explore whether quercetin, natural polyphenol, could alleviate seizure-induced neuron death preserve by inhibiting Nrf2-mediated ferroptosis.Kainic acid-induced epileptic mice model, morris water maze (MWM) test, cell counting kit-8 (CCK-8) assays, western blotting analysis, enzyme-linked immunosorbent assay, flow cytometry, quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence staining, RNA sequencing analysis were employed mechanisms which quercetin exerts protective effects on kainic model glutamate-induced HT22 neuronal death.Our findings suggested association between seizures clinical setting. Quercetin pretreatment alleviates seizure-like behaviors KA-induced mice. Additionally, vitro, co-treatment effectively neuroprotective death. These also closely pathway. Furthermore, bioinformatic profiling revealed that SIRT1/Nrf2/SLC7A11/GPX4 plays crucial role Glu-induced pretreated quercetin.These indicated protects against vivo vitro via

Language: Английский

Citations

87

Resveratrol and Immune Cells: A Link to Improve Human Health DOI Creative Commons
Alessio Alesci, Noemi Nicosia, Angelo Fumia

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(2), P. 424 - 424

Published: Jan. 10, 2022

The use of polyphenols as adjuvants in lowering risk factors for various debilitating diseases has been investigated recent years due to their possible antioxidant action. Polyphenols represent a fascinating and relatively new subject research nutraceuticals nutrition, with interest rapidly expanding since they can help maintain health by controlling metabolism, weight, chronic diseases, cell proliferation. Resveratrol is phenolic compound found mostly the pulp, peels, seeds, stems red grapes. It wide variety biological actions that be used prevent beginning or manage symptoms. influence multiple inflammatory non-inflammatory responses, protecting organs tissues, thanks its interaction immune cells activity on SIRT1. This anti-inflammatory, antioxidant, anti-apoptotic, neuroprotective, cardioprotective, anticancer, antiviral properties, making it potential adjunct traditional pharmaceutical therapy public health. review aims provide comprehensive analysis resveratrol terms active effects mechanism action modifying cellular response promote human psychophysical

Language: Английский

Citations

77

Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response DOI Creative Commons
V.О. Kostenko, O. Ye. Akimov, O.M. Gutnik

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(5), P. e15551 - e15551

Published: April 16, 2023

One of the adverse outcomes acute inflammatory response is progressing to chronic stage or transforming into an aggressive process, which can develop rapidly and result in multiple organ dysfunction syndrome. The leading role this process played by Systemic Inflammatory Response that accompanied production pro- anti-inflammatory cytokines, phase proteins, reactive oxygen nitrogen species.The purpose review highlights both recent reports results authors' own research encourage scientists new approaches differentiated therapy various SIR manifestations (low- high-grade systemic phenotypes) modulating redox-sensitive transcription factors with polyphenols evaluate saturation pharmaceutical market appropriate dosage forms tailored for targeted delivery these compounds.Redox-sensitive such as NFκB, STAT3, AP1 Nrf2 have a mechanisms formation low- phenotypes variants SIR. These phenotypic underlie pathogenesis most dangerous diseases internal organs, endocrine nervous systems, surgical pathologies, post-traumatic disorders.The use individual chemical compounds class polyphenols, their combinations be effective technology Administering natural oral very beneficial management number low-grade phenotype. associated phenotype requires medicinal phenol preparations manufactured parenteral administration.

Language: Английский

Citations

56

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences DOI Open Access
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Celia Andrés

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2600 - 2600

Published: Feb. 23, 2024

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between oxygen and nitrogen species in the body its ability to neutralize them. These generated by both internal external factors can damage cellular lipids, proteins, DNA. Antioxidants prevent or slow down oxidation process interrupting transfer of electrons substances agents. This is particularly important at level because reactions lead formation FR contribute various diseases. As we age, RS accumulates leads organ dysfunction age-related disorders. Polyphenols; vitamins A, C, E; selenoproteins possess antioxidant properties may have a role preventing treating certain human diseases associated with RS. In this review, explore current evidence on potential benefits dietary supplementation investigate intricate connection SIRT1, crucial regulator aging longevity; transcription factor NRF2; polyphenols, vitamins, selenium. Finally, discuss positive effects molecules, such as reducing RS, their slowing several

Language: Английский

Citations

40

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing DOI Creative Commons
Yuqing Liu, Yejun Tan, Zheyu Zhang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and characterised by systemic changes in both intracellular extracellular microenvironments that affect the entire body instead of single organ. Understanding specific mechanisms underlying role ageing development can facilitate treatment ageing-related diseases, such as AD. Signs brain have been observed AD patients animal models. Alleviating pathological caused dramatically ameliorate amyloid beta- tau-induced neuropathological memory impairments, indicating plays pathophysiological process In this review, we summarize impact several age-related factors on propose preventing promising strategy improving cognitive health.

Language: Английский

Citations

33

Emerging roles of SIRT1 activator, SRT2104, in disease treatment DOI Creative Commons
Ning Chang, Junyang Li,

Sufen Lin

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 6, 2024

Abstract Silent information regulator 1 (SIRT1) is a NAD + -dependent class III deacetylase that plays important roles in the pathogenesis of numerous diseases, positioning it as prime candidate for therapeutic intervention. Among its modulators, SRT2104 emerges most specific small molecule activator SIRT1, currently advancing into clinical translation phase. The primary objective this review to evaluate emerging SRT2104, and explore potential agent various diseases. In present review, we systematically summarized findings from an extensive array literature sources including progress application disease treatment molecular mechanisms by reviewing published databases such PubMed, Web Science, World Health Organization International Clinical Trials Registry Platform. We focuses on strides made employing treatment, elucidating underpinnings based preclinical research data. reveal potent SIRT1 activator, holds considerable potential, particularly modulating metabolic longevity-related pathways. This establishes leading with significant promise.

Language: Английский

Citations

28

Synergistic Neuroprotection Through Epigenetic Modulation by Combined Curcumin-Enriched Turmeric Extract and L-Ascorbic Acid in Oxidative Stress-Induced SH-SY5Y Cell Damage DOI Creative Commons
Jurairat Khongrum, Nootchanat Mairuae, Tongjit Thanchomnang

et al.

Foods, Journal Year: 2025, Volume and Issue: 14(5), P. 892 - 892

Published: March 5, 2025

Epigenetic modulation plays a crucial role in neuroprotection by regulating cellular responses to stress, inflammation, and oxidative damage, particularly neurodegenerative diseases. Recognizing the therapeutic potential of epigenetic regulators, this study investigated synergistic neuroprotective effects curcumin-enriched turmeric extract combined with L-ascorbic acid, focusing on its pathways stress-induced neuronal damage. SH-SY5Y cells were treated combination at 20 40 µg/mL, subsequently exposed 200 µM hydrogen peroxide (H2O2) induce stress. Cell viability was assessed using MTT assay, while mechanisms evaluated analyzing markers modulation, apoptosis. The significantly enhanced cell viability, upregulated sirtuin-1 (SIRT1), reduced DNA methyltransferase 1 (DNMT1) expression, indicating effective modulation. Enhanced antioxidant defenses observed, as evidenced increased activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), along decreased malondialdehyde (MDA) reactive oxygen species (ROS) levels, alleviating Additionally, it suppressed nuclear factor kappa B (NF-κB) activity downstream mediator interleukin-6 (IL-6), thereby mitigating inflammation. treatment also anti-apoptotic Bcl-2 expression reducing pro-apoptotic markers, including caspase-3 caspase-9, suggesting inhibition intrinsic apoptotic pathway. These findings highlight novel combination, demonstrating ability modulate suppressing preventing undesired Its multifaceted properties make promising functional ingredient foods for disease intervention. However, further investigations, animal studies clinical trials, are essential evaluate safety potential.

Language: Английский

Citations

2

SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close DOI Creative Commons
Gaber El‐Saber Batiha, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Inflammopharmacology, Journal Year: 2022, Volume and Issue: 31(1), P. 37 - 56

Published: Dec. 29, 2022

Abstract Silent information regulator (SIRT) has distinctive enzymatic activities and physiological functions to control cell-cycle progression, gene expression, DNA stability by targeting histone non-histone proteins. SIRT1 enhances synaptic formation activity, therefore, can reduce the progression of various degenerative brain diseases including Parkinson’s disease (PD). activity is decreased aging with a subsequent increased risk for development diseases. Inhibition promotes inflammatory reactions since inhibits transcription nuclear factor kappa B (NF-κB) which also activation via microRNA miR-34a NAD synthesis. highly expressed in microglia as well neurons, antioxidant anti-inflammatory effects. Therefore, this review aimed find possible role PD neuropathology. neuroprotective effects; downregulation during p53 expression may increase vulnerability neuronal cell deaths. neuropathology linked sequence changes release pro-inflammatory cytokines due signaling pathways. In addition, oxidative stress, disorders, mitochondrial dysfunction, apoptosis contribute mutually Thus, activators play crucial mitigation through amelioration apoptosis,

Language: Английский

Citations

68

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases DOI Creative Commons

Chenxi Lu,

Huadong Zhao,

Yanqing Liu

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 19(2), P. 484 - 501

Published: Dec. 19, 2022

Silent information regulator 1 (SIRT1), a highly conserved NAD+-dependent deacetylase, is cellular that has received extensive attention in recent years and regarded as sensor of energy metabolism. The accumulated evidence suggests SIRT1 involved the development endocrine metabolic diseases. In variety organisms, regulates gene expression through deacetylation histone, transcription factors, lysine residues other modified proteins including several signal thereby enhancing therapeutic effects These evidences indicate targeting promising applications treatment This review focuses on role First, we describe background structure SIRT1. Then, outline diseases such hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, polycystic ovarian syndrome. Subsequently, agonists inhibitors above are summarized future research directions proposed. Overall, presents here may highlight potential biomarker target for

Language: Английский

Citations

65