Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Март 1, 2024

Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) its post-translational modifications, especially sumoylation, crucial in understanding the progression AD exploring novel therapeutic avenues. This study investigates impact exercise on sumoylation IGF1R role ameliorating symptoms APP/PS1 mice, with specific focus neuroinflammation innovative strategies. mice were subjected to regimen moderate-intensity exercise. investigation encompassed assessments functions, alterations hippocampal protein expressions, neuroinflammatory markers, effects SUMO1 nuclear translocation. Additionally, evaluated efficacy KPT-330, export inhibitor, as an alternative Exercise notably enhanced functions possibly through modulations proteins, including Bcl-2 BACE1. A decrease markers such IL-1β, IL-6, TNF-α was observed, indicative reduced modulated translocation hippocampus, thereby facilitating neuronal regeneration. Mutant (MT IGF1R), lacking modification sites, showed SUMOylation, leading diminished expression pro-inflammatory cytokines apoptosis. KPT-330 impeded formation IGF1R/RanBP2/SUMO1 complex, limiting translocation, inflammation, apoptosis, while enhancing neuron proliferation. Moderate-intensity effectively mitigates disease (AD) primarily diminishing neuroinflammation, reduction Sumoylation. potential physical exercise, enhances neuroprotective inhibiting SUMOylation targeting XPO1, presenting promising strategy for AD.

Язык: Английский

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(8), С. 3327 - 3361

Опубликована: Май 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Язык: Английский

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Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00525 - e00525

Опубликована: Янв. 1, 2025

Язык: Английский

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Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июнь 15, 2023

Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 triggers the expression NF-κB NLRP3 inflammasomes, inducing pyroptosis inflammatory response. However, whether mtDNA induces NPC via TLR9-NF-κB-NLRP3 axis promotes IVDD remains uncertain.We constructed an vitro oxidative stress injury model to clarify mechanism release, TLR9-NF-κB signaling pathway activation, injury. We further verified action underlying inhibition release or activation vitro. then rat punctured understand inhibiting IVDD.We used human NP specimen assays show that levels TLR9, NF-κB, inflammasomes correlated with degree IVDD. demonstrated mediated stress-induced Oxidative damage mitochondria NPCs, causing opening permeability transition pores (mPTP) leading into cytosol. Furthermore, mPTP blocked thereby IVDD.mtDNA plays key role mediating axis. Our findings provide new potential targets for

Язык: Английский

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The cGAS-STING pathway: a therapeutic target in diabetes and its complications

Burns & Trauma, Год журнала: 2024, Номер 12

Опубликована: Янв. 1, 2024

Diabetic wound healing (DWH) represents a major complication of diabetes where inflammation is key impediment to proper healing. The cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) signaling pathway has emerged as central mediator inflammatory responses cell stress and damage. However, the contribution cGAS-STING activation impaired in DWH remains understudied. In this review, we examine evidence that cGAS-STING-driven critical factor underlying defective DWH. We summarize studies revealing upregulation diabetic wounds discuss how exacerbates senescence disrupts cellular metabolism block Partial pharmaceutical inhibition shown promise damping improving preclinical models. highlight knowledge gaps regarding DWH, including its relationships with endoplasmic reticulum metal-ion signaling. Elucidating these mechanisms may unveil new therapeutic targets within improve outcomes This review synthesizes current understanding contributes pathology proposes future research directions exploit modulation for benefit.

Язык: Английский

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The potential influence of melatonin on mitochondrial quality control: a review

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 11, 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of homeostasis functional recovery after injury coordinated by biogenesis, dynamics autophagy, which collectively referred to as quality control. There increasing evidence that mitochondria important targets melatonin exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported metabolized in mitochondria. In this review, we summarize the role damaged elimination energy supply regulating control, may provide new strategies clinical treatment mitochondria-related diseases.

Язык: Английский

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Therapeutic role of PTEN in tissue regeneration for management of neurological disorders: stem cell behaviors to an in-depth review

Cell Death and Disease, Год журнала: 2024, Номер 15(4)

Опубликована: Апрель 16, 2024

Abstract Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) represents the initial tumor suppressor gene identified to possess phosphatase activity, governing various cellular processes including cell cycle regulation, migration, metabolic pathways, autophagy, oxidative stress response, senescence. Current evidence suggests that PTEN is critical for stem maintenance, self-renewal, lineage commitment, differentiation. Based latest available evidence, we provide a comprehensive overview of mechanisms by which regulates activities different populations influences neurological disorders, encompassing autism, stroke, spinal cord injury, traumatic brain Alzheimer’s disease Parkinson’s disease. This review aims elucidate therapeutic impacts in relation neurogenesis or niche across range offering foundation innovative approaches aimed at tissue repair regeneration disorders.

Язык: Английский

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Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

Brain Sciences, Год журнала: 2023, Номер 13(4), С. 632 - 632

Опубликована: Апрель 7, 2023

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer's. Microglia are the brain's primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds anti-inflammatory antioxidant properties, epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related diseases involving activated microglia cells. The objective of current study was to examine molecular targets underlying effects EGCG in BV-2 cells were grown, stimulated, treated EGCG. Cytotoxicity nitric oxide (NO) production evaluated. Immunoassay, PCR array, WES™ Technology utilized evaluate inflammatory, neuroprotective modulators well signaling pathways involved mechanistic action neuroinflammation. Our findings showed that significantly inhibited mediator NO LPS-stimulated In addition, ELISA analysis revealed decreases cytokine IL-6 while it increases TNF-α. array downregulated MIF, CCL-2, CSF2. It also upregulated IL-3, IL-11, TNFS10. Furthermore, inflammatory mRNA expression mTOR, NF-κB2, STAT1, Akt3, CCL5, SMAD3 upregulating Ins2, Pld2, A20/TNFAIP3, GAB1. Additionally, reduced relative protein Akt3. These suggest be used its prevent diseases.

Язык: Английский

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Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 735 - 735

Опубликована: Апрель 24, 2023

An NAD+-dependent deacetylase called Sirtuin 3 (Sirt3) is involved in the metabolic processes of mitochondria, including energy generation, tricarboxylic acid cycle, and oxidative stress. Sirt3 activation can slow down or prevent mitochondrial dysfunction response to neurodegenerative disorders, demonstrating a strong neuroprotective impact. The mechanism illnesses has been elucidated over time; it essential for neuron, astrocyte, microglial function, its primary regulatory factors include antiapoptosis, stress, maintenance homeostasis. Neurodegenerative such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), multiple (MS), may benefit from thorough in-depth investigation Sirt3. In this review, we primarily cover Sirt3’s role regulation nerve cells connection between disorders.

Язык: Английский

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Therapeutic role of curcumin in adult neurogenesis for management of psychiatric and neurological disorders: a scientometric study to an in-depth review

Critical Reviews in Food Science and Nutrition, Год журнала: 2022, Номер 63(28), С. 9379 - 9391

Опубликована: Апрель 28, 2022

Aberrant neurogenesis is a major factor in psychiatric and neurological disorders that have significantly attracted the attention of neuroscientists. Curcumin primary constituent curcuminoid exerts several positive pharmacological effects on aberrant neurogenesis. First, it important to understand different processes neurogenesis, whether their dysfunction promotes etiology as well development many disorders; then investigate mechanisms by which curcumin affects an active participant pathophysiological events. Based scientometric studies additional extensive research, we explore regulates adult turn diseases, i.e., depression among them traumatic brain injury (TBI), stroke, Alzheimer's disease (AD), Gulf War Illness (GWI) Fragile X syndrome (FXS). This review aims elucidate therapeutic various disorders. Specifically, discuss regulatory role activities neural stem cells (NSCs), including proliferation, differentiation, migration NSCs. geared toward providing novel application prospects treating regulating

Язык: Английский

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