The Beneficial Roles of SIRT1 in Neuroinflammation-Related Diseases

Oxidative Medicine and Cellular Longevity, Год журнала: 2020, Номер 2020, С. 1 - 19

Опубликована: Сен. 16, 2020

Sirtuins are the class III of histone deacetylases whose deacetylate histones is dependent on nicotinamide adenine dinucleotide (NAD+). Among seven sirtuins, SIRT1 plays a critical role in modulating wide range physiological processes, including apoptosis, DNA repair, inflammatory response, metabolism, cancer, and stress. Neuroinflammation associated with many neurological diseases, ischemic stroke, bacterial infections, traumatic brain injury, Alzheimer’s disease (AD), Parkinson’s (PD). Recently, numerous studies indicate protective effects neuroinflammation-related diseases. Here, we review latest progress regarding anti-inflammatory neuroprotective SIRT1. First, introduce structure, catalytic mechanism, functions Next, discuss molecular mechanisms regulation neuroinflammation. Finally, analyze several common neuroinflammation-associated such as cerebral ischemia, spinal cord AD, PD. Taken together, this information implies that may serve promising therapeutic target for treatment disorders.

Язык: Английский

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Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Ноя. 30, 2023

Inflammation is a fundamental defensive response to harmful stimuli, but the overactivation of inflammatory responses associated with most human diseases. Reactive oxygen species (ROS) are class chemicals that generated after incomplete reduction molecular oxygen. At moderate levels, ROS function as critical signaling molecules in modulation various physiological functions, including responses. However, at excessive exert toxic effects and directly oxidize biological macromolecules, such proteins, nucleic acids lipids, further exacerbating development causing Therefore, designing manufacturing biomaterials scavenge has emerged an important approach for restoring homeostasis, limiting protecting host against damage. This review systematically outlines dynamic balance production clearance under conditions. We focus on mechanisms by which regulate cell proteins how these affect inflammation. Furthermore, we discuss use potential currently available-biomaterials ROS, agents were engineered reduce levels blocking generation, chemically reacting or catalytically accelerating clearance, treatment Finally, evaluate challenges prospects controlled material design scavenging biomaterials.

Язык: Английский

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Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

Antioxidants, Год журнала: 2022, Номер 11(12), С. 2377 - 2377

Опубликована: Ноя. 30, 2022

Cerebral ischemic stroke is characterized by acute ischemia in a certain part of the brain, which leads to brain cells necrosis, apoptosis, ferroptosis, pyroptosis, etc. At present, there are limited effective clinical treatments for cerebral stroke, and recovery blood circulation will lead ischemia-reperfusion injury (CIRI). involves many pathological processes such as oxidative stress, inflammation, mitochondrial dysfunction. Nuclear factor erythroid 2-related 2 (Nrf2), one most critical antioxidant transcription factors cells, can coordinate various cytoprotective inhibit stress. Targeting Nrf2 considered potential strategy prevent treat injury. During ischemia, participates signaling pathways Keap1, PI3K/AKT, MAPK, NF-κB, HO-1, then alleviates or CIRI inhibiting anti-inflammation, maintaining homeostasis, protecting blood–brain barrier, ferroptosis. In this review, we have discussed structure Nrf2, mechanisms related research on treatment through pathway recent years, expounded important role future stroke.

Язык: Английский

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Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Дек. 7, 2021

Periodontitis (PD) is a common chronic infectious disease. The local inflammatory response in the host may cause destruction of supporting periodontal tissue. Macrophages play variety roles PD, including regulatory and phagocytosis. Moreover, under induction different factors, macrophages polarize form functional phenotypes. Among them, M1-type with proinflammatory functions M2-type anti-inflammatory are most representative, both them can regulate tendency immune system to exert or functions. M1 M2 involved destructive reparative stages PD. Due complex microenvironment dynamic development various mediators, increasing attention has been given study macrophage polarization This review summarizes role PD its research progress.

Язык: Английский

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Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression

Life Sciences, Год журнала: 2021, Номер 278, С. 119499 - 119499

Опубликована: Апрель 16, 2021

Язык: Английский

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Involvement of p38 MAPK in Synaptic Function and Dysfunction

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(16), С. 5624 - 5624

Опубликована: Авг. 6, 2020

Many studies have revealed a central role of p38 MAPK in neuronal plasticity and the regulation long-term changes synaptic efficacy, such as potentiation (LTP) depression (LTD). However, is classically known responsive element to stress stimuli, including neuroinflammation. Specific pathophysiology Alzheimer’s disease (AD), several shown that cascade activated either response Aβ peptide or presence tauopathies. Here, we describe its implication an animal model neurodegeneration. In particular, recent evidence suggests α isoform potential neurotherapeutic target, specific inhibitors been developed proven be effective ameliorating memory deficits AD mouse models.

Язык: Английский

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Targeting the ERK Signaling Pathway in Melanoma

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(6), С. 1483 - 1483

Опубликована: Март 25, 2019

The discovery of the role RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era treatment this tumor. Vemurafenib was first specific kinase inhibitor approved for therapy advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib encorafenib. However, despite excellent results first-generation inhibitors terms response rate, average duration short, due to onset genetic epigenetic resistance mechanisms. combination with MEK is an strategy circumvent drug resistance, additional advantage reducing side effects paradoxical reactivation MAPK pathway. recent development RAS extracellular signal-related kinases (ERK) promises add players ultimate suppression signaling control pathway-related resistance. In review, we analyze pharmacological, preclinical, clinical trial data various inhibitors, keen interest their applicability management melanoma.

Язык: Английский

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Neuronal cell death mechanisms in Alzheimer’s disease: An insight

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Авг. 25, 2022

Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression protein activity responsible for normal development as well maintenance tissue homeostasis. Aberrant activation this pathway results by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent death. Such pathological changes neurons alone or combination have been observed the pathogenesis neurodegenerative diseases Alzheimer’s disease (AD). Pathological hallmarks AD focus primarily on accumulation two main markers: amyloid β peptides abnormally phosphorylated tau proteins. These aggregates result formation A-β plaques neuro-fibrillary tangles (NFTs) induce neuroinflammation neurodegeneration over years to decades leading a multitude cognitive behavioral deficits. Autopsy findings reveal massive neuronal manifested form cortical volume shrinkage, reduction sizes gyri up 50% increase sulci. Multiple forms recorded from different studies conducted so far. However, understanding mechanism/s patients remains mystery trigger that aberrant RCD unknown because limited availability dying neurons. This review attempts elucidate process death, how it gets unregulated response intra extracellular stressors, their interplay role Disease human experimental models AD. Further we plan explore correlation amyloid-beta Tau with loss seen

Язык: Английский

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Microglia Mediated Neuroinflammation in Parkinson’s Disease

Cells, Год журнала: 2023, Номер 12(7), С. 1012 - 1012

Опубликована: Март 25, 2023

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in elderly. Tremor, shaking, movement problems, and difficulty with balance coordination are among hallmarks, dopaminergic neuronal loss substantia nigra pars compacta of brain aggregation intracellular protein α-synuclein pathological characterizations. Neuroinflammation has emerged as an involving mechanism at initiation development PD. It a complex network interactions comprising immune non-immune cells addition to mediators response. Microglia, resident macrophages CNS, take on leading role regulating neuroinflammation maintaining homeostasis. Under normal physiological conditions, they exist “homeostatic” but upon stimuli, switch “reactive state”. Pro-inflammatory (M1) anti-inflammatory (M2) phenotypes used classify microglial activity each phenotype having its own markers released mediators. When M1 microglia persistent, will contribute various inflammatory diseases, including such In this review, we focus mediated PD also signaling pathways, receptors, involved process, presenting studies that associate microglia-mediated inflammation A better understanding important seeking new therapies for possibly other diseases.

Язык: Английский

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Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation

Current Molecular Medicine, Год журнала: 2021, Номер 23(1), С. 13 - 35

Опубликована: Дек. 24, 2021

Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free ultimately leads to oxidative stress causing oxidation damage significant macromolecules the living system essentially disrupting signal transduction pathways antioxidants equilibrium. At lower concentrations, ROS serves as "second messengers," influencing many physiological processes cell. However, higher concentrations beyond cell capacity cause stress, contributing human pathologies such diabetes, cancer, Parkinson's disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, Alzheimer's disease. Signaling NF-κB, MAPKs, PI3K/Akt/ mTOR, Keap1-Nrf2- ARE modulate detrimental effects by increasing expression cellular antioxidant defenses, phase II detoxification enzymes, decreased production ROS. H2O2 are indeed needed for advancement cycle molecules influence DNA, proteins, enzymes pathway. In course progression, redox environment becomes oxidized, moving from G1 phase, becoming G2/M moderate S phase. Signals form an increase pro-oxidant levels required, signals often terminated a rise amount MnSOD with decrease level cyclin D1 proteins. Therefore, understanding mechanism regulation will help therapy diseases.

Язык: Английский

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