Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 816 - 816

Опубликована: Май 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Язык: Английский

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Neurotoxicity of fine and ultrafine particulate matter: A comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework

The Science of The Total Environment, Год журнала: 2024, Номер 947, С. 174450 - 174450

Опубликована: Июль 3, 2024

Язык: Английский

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Nutrition and autophagy deficiency in critical illness

Current Opinion in Critical Care, Год журнала: 2023, Номер 29(4), С. 306 - 314

Опубликована: Июнь 8, 2023

Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to high risk multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. discusses insight into role autophagy in involvement artificial feeding insufficient activation Recent findings Animal studies manipulating have shown its protective effects against kidney, lung, liver, intestinal injury after several insults. also protected peripheral, respiratory, cardiac muscle despite aggravated atrophy. Its acute brain is more equivocal. patient showed that suppressed illness, particularly protein/amino acid doses. Feeding-suppressed may explain short long-term harm by early enhanced calorie/protein large randomized controlled trials. Summary Insufficient at least partly explained feeding-induced suppression. why nutrition failed benefit critically ill patients or even induced harm. Safe, specific avoiding prolonged starvation opens perspectives for improving outcomes

Язык: Английский

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The Metabolic Basis for Nervous System Dysfunction in Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease

Current Neurovascular Research, Год журнала: 2023, Номер 20(3), С. 314 - 333

Опубликована: Июль 25, 2023

Disorders of metabolism affect multiple systems throughout the body but may have greatest impact on both central and peripheral nervous systems. Currently available treatments behavior changes for disorders that include diabetes mellitus (DM) system diseases are limited cannot reverse disease burden. Greater access to healthcare a longer lifespan led an increased prevalence metabolic neurodegenerative disorders. In light these challenges, innovative studies into underlying pathways offer new treatment perspectives Alzheimer's Disease, Parkinson's Huntington's Disease. Metabolic intimately tied can lead debilitating outcomes, such as multi-nervous disease, susceptibility viral pathogens, long-term cognitive disability. Novel strategies robustly address involve careful consideration cellular metabolism, programmed cell death pathways, mechanistic target rapamycin (mTOR) its associated mTOR Complex 1 (mTORC1), 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, risk factors apolipoprotein E (APOE-ε4) gene. Yet, complex necessitate comprehensive understanding achieve clinical outcomes susceptibility, onset, progression.

Язык: Английский

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Nano-enhanced nature medicine for ischemic stroke: Opportunities and challenges

Biomedical Technology, Год журнала: 2024, Номер 7, С. 32 - 45

Опубликована: Июль 16, 2024

Ischemic stroke (IS), a major cause of death and disability globally, requires innovative therapeutic approaches due to its complex pathology. Nature medicine (NM) offers promising treatments through bioactive compounds, which target the multifaceted nature stroke-induced damage. However, clinical application NM is limited by challenges in bioavailability specificity. This review article presents an advanced perspective on integrating nanotechnology with create potent nanodelivery systems for ischemic treatment. We highlight pathological underpinnings stroke, including oxidative stress, inflammation, apoptosis, discuss how compounds offer targeted mitigation strategies. By incorporating platforms, such as liposomes nanoparticles, these -based can achieve enhanced targeting, solubility, controlled release, significantly improving outcomes while reducing side effects. Despite developments, translation nano-enhanced into practice faces obstacles, manufacturing scalability, regulatory approval, safety evaluations. emphasizes potential combining advance therapy, calling integrated research efforts overcome existing barriers fully realize benefits this approach.

Язык: Английский

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IGF-PLGA microspheres promote angiogenesis and accelerate skin flap repair and healing by inhibiting oxidative stress and regulating the Ang 1/Tie 2 signaling pathway

European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 193, С. 106687 - 106687

Опубликована: Янв. 2, 2024

Random flaps are widely used in the treatment of injuries, tumors, congenital malformations, and other diseases. However, postoperative skin prone to ischemic necrosis, leading surgical failure. Insulin-like growth factor- 1(IGF-1) belongs IGF family exerts its growth-promoting effects various tissues through autocrine or paracrine mechanisms. Its application traumatic diseases is relatively limited. Poly (lactic-co-glycolic acid) (PLGA) a degradable high-molecular-weight organic compound commonly biomaterials. This study prepared IGF-PLGA sustained-release microspheres explore their impact on survival rate both vitro vivo, as well mechanisms involved. The research results demonstrate that has good effect. At cellular level, it can promote 3T3 cell proliferation by inhibiting oxidative stress, inhibit apoptosis, enhance tube formation ability human umbilical vein endothelial cells (HUVEC) . animal accelerates flap healing promoting vascularization inhibition stress. Furthermore, this reveals role activating Angiopoietin-1(Ang1)/Tie2 signaling pathway vascularization, providing strong theoretical basis therapeutic target for IGF-1

Язык: Английский

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Cognitive Impairment in Multiple Sclerosis

Bioengineering, Год журнала: 2023, Номер 10(7), С. 871 - 871

Опубликована: Июль 23, 2023

Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.

Язык: Английский

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GLP-1(7–36) protected against oxidative damage and neuronal apoptosis in the hippocampal CA region after traumatic brain injury by regulating ERK5/CREB

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Фев. 19, 2024

Abstract Background Glucagon-like peptide-1 (GLP-1) (7–36) amide, an endogenous active form of GLP-1, has been shown to modulate oxidative stress and neuronal cell survival in various neurological diseases. Objective This study investigated the potential effects GLP-1(7–36) on apoptosis cells following traumatic brain injury (TBI) explored underlying mechanisms. Methods Traumatic models were established male SD rats for vivo experiments. The extent cerebral oedema was assessed using wet-to-dry weight ratios intervention. Neurological dysfunction cognitive impairment evaluated through behavioural Histopathological changes observed haematoxylin eosin staining. Oxidative levels hippocampal tissues measured. TUNEL staining Western blotting employed examine apoptosis. In vitro experiments neural ERK5 phosphorylation activation. Immunofluorescence colocalization p-ERK5 NeuN analysed immunofluorescence cytochemistry. Results Rats with TBI exhibited deterioration, increased stress, enhanced apoptosis, which ameliorated by treatment. Notably, induced rats. However, upon inhibition, elevated, even presence GLP-1(7–36). Conclusion summary, this suggested that suppressed damage after activating ERK5/CREB.

Язык: Английский

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AZD6738 Attenuates LPS-Induced Corneal Inflammation and Fibrosis by Modulating Macrophage Function and Polarization

Inflammation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

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Microglial Autophagic Dysregulation in Traumatic Brain Injury: Molecular Insights and Therapeutic Avenues

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Traumatic brain injury (TBI) is a complex and multifaceted condition that can result in cognitive behavioral impairments. One aspect of TBI has received increasing attention recent years the role microglia, brain-resident immune cells, pathophysiology injury. Specifically, evidence suggests dysfunction microglial autophagy, process by which cells degrade recycle their own damaged components, may contribute to development progression TBI-related Here, we unravel pathways microglia autophagic dysregulation predisposes secondary damage neurological deficits following TBI. An overview perpetuation worsening inflammatory response, neuroinflammation, neuronal cell death follows. Further, have evaluated several signaling processes autophagy dysfunction-mediated inflammation, neurodegeneration, poor outcome Additionally, discussion on small molecule therapeutics employed modulate these mechanisms treat been presented. However, additional research required fully understand behind underlying uncover potential therapeutic targets for restoring failure

Язык: Английский

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