Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101803 - 101803

Published: Nov. 19, 2020

Imbalances in redox homeostasis can result oxidative stress, which is implicated various pathological conditions including the fatal neuromuscular disease Duchenne Muscular Dystrophy (DMD). DMD a complicated disease, with many druggable targets at cellular and molecular level calcium-mediated muscle degeneration; mitochondrial dysfunction; stress; inflammation; insufficient regeneration dysregulated protein organelle maintenance. Previous investigative therapeutics tended to isolate focus on just one of these and, consequently, therapeutic activity has been limited. Nuclear erythroid 2-related factor 2 (Nrf2) transcription that upregulates cytoprotective gene products response oxidants other toxic stressors. Unlike strategies, targeted Nrf2 activation potential simultaneously modulate separate features amplify benefits. Here, we review literature providing theoretical context for targeting as modifying treatment against DMD.

Language: Английский

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Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 88, P. 102003 - 102003

Published: Aug. 6, 2024

Ageing is associated with mitochondrial dysfunction and increased oxidative stress. Exercise generates endogenous reactive oxygen species (ROS) promotes rapid remodelling. We investigated the role of Peroxiredoxin 2 (PRDX-2) in adaptations to exercise ageing using Caenorhabditis elegans as a model system. PRDX-2 was required for remodelling response mediated by DAF-16 transcription factor activation regulation fusion gene eat-3. Employing an acute recovery cycle, we demonstrated exercise-induced ER contact sites (MERCS) assembly dependent on signalling. There fragmentation, elevated ROS altered redox state concomitant impaired nuclear localisation during ageing. Similarly, prdx-2 mutant strain exhibited fragmentation failure activate fusion. Collectively, our data highlight critical orchestrating physiological stress regulating localisation.

Language: Английский

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Changes of Gene Expression Patterns of Muscle Pathophysiology-Related Transcription Factors During Denervated Muscle Atrophy

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: June 24, 2022

Peripheral nerve injury is common, and can lead to skeletal muscle atrophy dysfunction. However, the underlying molecular mechanisms are not fully understood. The transcription factors have been proved play a key role in denervated atrophy. In order systematically analyze obtain more comprehensive information of regulatory atrophy, new transcriptome survey focused on warranted. current study, we used microarray identify differentially expressed genes encoding rat model sciatic dissection. Gene Ontology Kyoto Encyclopedia Genes Genomes analyses were explore biological functions their target related pathophysiology. We found that mainly involved immune response. Based correlation analysis expression trends factors, 18 identified. Stat3, Myod1, Runx1, Atf3, Junb, Runx2, Myf6, Stat5a, Tead4, Klf5, Myog, Mef2a, Hes6 upregulated. Ppargc1a, Nr4a1, Lhx2, Ppara, Rxrg downregulated. Functional network mapping revealed these inflammation, development, aging, proteolysis, differentiation, regeneration, autophagy, oxidative stress, ubiquitination. These findings may help understand provide potential targets for future therapeutic interventions following peripheral injury.

Language: Английский

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Restoration of CPEB4 prevents muscle stem cell senescence during aging

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(15), P. 1383 - 1398.e6

Published: June 15, 2023

Age-associated impairments in adult stem cell functions correlate with a decline somatic tissue regeneration capacity. However, the mechanisms underlying molecular regulation of aging remain elusive. Here, we provide proteomic analysis physiologically aged murine muscle cells (MuSCs), illustrating pre-senescent signature. During aging, mitochondrial proteome and activity are impaired MuSCs. In addition, inhibition function results cellular senescence. We identified an RNA-binding protein, CPEB4, downregulated various tissues, which is required for MuSC functions. CPEB4 regulates through translational control. MuSCs devoid induced Importantly, restoring expression rescued metabolism, improved geriatric functions, prevented senescence human lines. Our findings basis possibility that metabolism to govern senescence, implication therapeutic intervention age-related

Language: Английский

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Artificial Intelligence (AI) and Ethics in Medicine at a Global Level: Benefits and Risks

Özgür Yayınları eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: June 21, 2023

Technological developments in medicine have created significant transformations healthcare services and offered more effective diagnosis treatment options for patients. Among these advances, artificial intelligence (AI) plays a pivotal role variety of medical applications, from disease planning to clinical research patient care optimization. However, the rapid development also raises ethical challenges concerns, including privacy, data security, inequality societal impacts. This study examines potential benefits risks associated with global use medicine. The presents examples features AI-based data-driven treatment, prediction early warning systems, personalized planning, drug discovery, telemedicine remote healthcare. Discussions confidentiality, fairness, integrity, transparency, autonomy, responsibility accountability, change management, social acceptance are emphasized, emphasizing importance rules guidelines AI An analysis publication trends ethics is presented, providing insights into most influential countries networks collaboration. As result, has enormous offers numerous benefits, better access healthcare, improved customized care, resource efficiency, prevention detection. related considerations must be addressed. Also, careful practices protection human factors vital leveraging full

Language: Английский

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Control of muscle satellite cell function by specific exercise‐induced cytokines and their applications in muscle maintenance

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(2), P. 466 - 476

Published: Feb. 20, 2024

Abstract Exercise is recognized to play an observable role in improving human health, especially promoting muscle hypertrophy and intervening mass loss‐related diseases, including sarcopenia. Recent rapid advances have demonstrated that exercise induces the release of abundant cytokines from several tissues (e.g., liver, muscle, adipose tissue), multiple improve functions or expand numbers adult stem cells, providing candidate for alleviating a wide range diseases. Muscle satellite cells (SCs) are population mitotically quiescent but exit dormancy state become activated response physical stimuli, after which SCs undergo asymmetric divisions generate new (stem cell pool maintenance) commit later differentiation into myocytes (skeletal replenishment). essential postnatal growth, maintenance, regeneration skeletal muscle. Emerging evidence reveals regulates function largely via exercise‐induced govern SC potential, this phenomenon complicated confusing. This review provides comprehensive integrative overview identified roles these function, more complete picture regarding mechanism homeostasis rejuvenation therapies

Language: Английский

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STAT3 inhibition recovers regeneration of aged muscles by restoring autophagy in muscle stem cells

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(8), P. e202302503 - e202302503

Published: June 6, 2024

Age-related reduction in muscle stem cell (MuSC) regenerative capacity is associated with cell-autonomous and non–cell-autonomous changes caused by alterations systemic skeletal environments, ultimately leading to a decline MuSC number function. Previous studies demonstrated that STAT3 plays key role driving expansion differentiation after injury-activated regeneration, regulating autophagy activated MuSCs. However, gradually declines MuSCs during lifespan contributes the impairment of MuSC-mediated regeneration aged muscles. Here, we show inhibition restores autophagic process MuSCs, thereby recovering ability promote geriatric mice. We could activate at nuclear level, promoting transcription autophagy-related genes, cytoplasmic targeting STAT3/PKR phosphorylation eIF2α. These results point as potential intervention reverse age-related block impairs regenerate They also reveal regulates function both transcription-dependent transcription-independent regulation autophagy.

Language: Английский

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STAT3 and STAT5 Activation in Solid Cancers

Published: Aug. 5, 2019

The Signal Transducer and Activator of Transcription (STAT)3 5 are activated by many cytokine receptors to regulate specific gene expression mitochondrial functions. Their role in cancer is largely context dependent as they can both act oncogenes tumor suppressors. We review here the STAT3/5 activation solid cancers summarize their association survival patients. molecular mechanisms that underpins oncogenic activity signaling includes regulation genes control cell cycle, death, inflammation stemness. In addition, STAT3 functions required for transformation. On other hand, several suppressor pathways on or including p19ARF/p53 pathway, tyrosine phosphatases, 1 3, sumo ligase PIAS3, E3 ubiquitin TMF/ARA160 miRNAs miR-124 miR-1181. Cancer mutations epigenetic alterations may alter balance between pro-oncogenic activities associated explaining progression human animal models.

Language: Английский

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Impaired phagocytic function in CX3CR1⁺ tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice

Aging Cell, Journal Year: 2020, Volume and Issue: 19(9)

Published: July 28, 2020

Abstract Skeletal muscle dysfunction in survivors of pneumonia disproportionately affects older individuals whom it causes substantial morbidity. We found that skeletal recovery was impaired old compared with young mice after influenza A virus‐induced pneumonia. In mice, loss associated expansion tissue‐resident macrophages and downregulation MHC II expression, followed by a proliferation satellite cells. These findings were absent deficient Cx3cr1 . Transcriptomic profiling from showed pathways phagocytosis proteostasis, persistent upregulation inflammatory pathways. Consistently, failed to downregulate MHCII expression during phagocytic function vitro Like animals, the receptor Mertk no macrophage expansion, downregulation, or cell recover Our data suggest CX3CR1 + population precludes

Language: Английский

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mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

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