Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7952 - 7952

Опубликована: Июль 21, 2024

Alzheimer's disease (AD) and Parkinson's (PD) are the most common neurodegenerative diseases, they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for treatment age-related diseases. Emerging evidence suggests that mitochondrial dysfunction reactive oxygen species (ROS) generation play central roles in onset progression Mitochondria key regulators respiratory function, cellular energy adenosine triphosphate production, maintenance redox homeostasis, which essential cell survival. Mitochondrial morphology function tightly regulated by maintaining balance among fission, fusion, biogenesis, mitophagy. In this review, we provide an overview main functions mitochondria, with focus on recent progress highlighting critical role ROS-induced oxidative stress, dysregulated dynamics, apoptosis, mitochondria-associated inflammation, impaired pathogenesis such as AD PD. We also discuss potential fusion biogenesis enhancers, fission inhibitors, mitochondria-targeted antioxidants drugs these

Язык: Английский

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Celecoxib ameliorates diabetic sarcopenia by inhibiting inflammation, stress response, mitochondrial dysfunction, and subsequent activation of the protein degradation systems

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Янв. 19, 2024

Aim: Diabetic sarcopenia leads to disability and seriously affects the quality of life. Currently, there are no effective therapeutic strategies for diabetic sarcopenia. Our previous studies have shown that inflammation plays a critical role in skeletal muscle atrophy. Interestingly, connection between chronic complications has been revealed. However, effects non-steroidal anti-inflammatory drug celecoxib on remains unclear. Materials Methods: The streptozotocin (streptozotocin)-induced model was established. Rotarod test grip strength were used assess function. Hematoxylin eosin immunofluorescence staining performed evaluate inflammatory infiltration morphology motor endplates muscles. Succinate dehydrogenase (SDH) determine number succinate dehydrogenase-positive fibers. Dihydroethidium levels reactive oxygen species (ROS). Western blot measure proteins involved inflammation, oxidative stress, endoplasmic reticulum ubiquitination, autophagic-lysosomal pathway. Transmission electron microscopy mitophagy. Results: Celecoxib significantly ameliorated atrophy, improving function preserving mice. also decreased cell, reduced IL-6 TNF-α, suppressed activation NF-κB, Stat3, NLRP3 inflammasome pathways levels, downregulated Nox2 Nox4, upregulated GPX1 Nrf2, further stress by inhibiting Perk-EIF-2α-ATF4-Chop inhibited Foxo3a, Fbx32 MuRF1 ubiquitin-proteasome system, as well BNIP3, Beclin1, ATG7, LC3Ⅱ protected mitochondria promoted mitochondrial biogenesis elevating SIRT1 PGC1-α, increased SDH-positive fibers Conclusion: improved protecting mitochondria, subsequently suppressing proteolytic systems. study provides evidences molecular mechanism treatment sarcopenia, broaden way new use

Язык: Английский

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Mitochondrial involvement in sarcopenia

Acta Physiologica, Год журнала: 2024, Номер 240(3)

Опубликована: Фев. 2, 2024

Abstract Sarcopenia lowers the quality‐of‐life for millions of people across world, as accelerated loss skeletal muscle mass and function contributes to both age‐ disease‐related frailty. Physical activity remains only proven therapy sarcopenia date, but alternatives are much sought after manage this progressive disorder in individuals who unable exercise. Mitochondria have been widely implicated etiology increasingly suggested attractive therapeutic targets help restore perturbed balance between protein synthesis breakdown that underpins atrophy. Reviewing current literature, we note mitochondrial bioenergetic changes generally interpreted intrinsic dysfunction renders cells incapable making sufficient ATP fuel synthesis. Based on reported effects interventions, however, argue observed may instead reflect an adaptation pathologically decreased energy expenditure sarcopenic muscle. Discrimination these mechanistic possibilities will be crucial improving management sarcopenia.

Язык: Английский

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Regenerative failure of sympathetic axons contributes to deficits in functional recovery after nerve injury

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

Renewed scientific interest in sympathetic modulation of muscle and neuromuscular junctions has spurred a flurry new discoveries with major implications for motor diseases. However, the role axons play persistent dysfunction that occurs after nerve injuries remains to be explored. Peripheral are common lead motor, sensory, autonomic deficits result lifelong disabilities. Given importance signaling metabolic health maintaining bodily homeostasis, it is imperative understand regenerative capacity injury. Therefore, we tested axon regeneration functional reinnervation skin muscle, both acute long-term, using battery anatomical, pharmacological, chemogenetic, cell culture, analytical chemistry, electrophysiological techniques. We employed several established growth-enhancing interventions, including electrical stimulation conditioning lesion, as well an innovative tool called bioluminescent optogenetics. Our results indicate not enhanced by any these treatments may even detrimental regeneration. Despite complete return sciatic injury, gastrocnemius atrophy cellular energy charge, measured relative ATP, ADP, AMP concentrations, persisted long stimulation. suggest long-term charge related deficiency New studies needed better mechanisms underlying develop therapeutics can enhance all types.

Язык: Английский

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Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses

Inflammation Research, Год журнала: 2025, Номер 74(1)

Опубликована: Янв. 13, 2025

Язык: Английский

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Cigarette Smoke Contributes to the Progression of MASLD: From the Molecular Mechanisms to Therapy

Cells, Год журнала: 2025, Номер 14(3), С. 221 - 221

Опубликована: Фев. 4, 2025

Cigarette smoke (CS), an intricate blend comprising over 4000 compounds, induces abnormal cellular reactions that harm multiple tissues. Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic (CLD), encompassing non-alcoholic (NAFL), steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Recently, the term NAFLD has been changed to metabolic dysfunction-associated steatotic (MASLD), NASH renamed (MASH). A multitude of experiments have confirmed association between CS incidence progression MASLD. However, specific signaling pathways involved need be updated with new scientific discoveries. exposure can disrupt lipid metabolism, induce inflammation apoptosis, stimulate fibrosis through promote Currently, there no officially approved efficacious pharmaceutical intervention in clinical practice. Therefore, lifestyle modifications emerged as primary therapeutic approach for managing Smoking cessation application series natural ingredients shown ameliorate pathological changes induced by CS, potentially serving effective decelerating MASLD development. This article aims elucidate which smoking promotes MASLD, while summarizing reversal factors identified recent studies, thereby offering novel insights future research on treatment

Язык: Английский

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Endoplasmic reticulum stress and unfolded protein response: Roles in skeletal muscle atrophy

Biochemical Pharmacology, Год журнала: 2025, Номер 234, С. 116799 - 116799

Опубликована: Фев. 12, 2025

Язык: Английский

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MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 30, 2024

Abstract Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli injuries, range stem/progenitor cells, with stem cells or satellite (MuSCs) being the predominant cell type, are rapidly activated repair regenerate skeletal within weeks. Under normal conditions, MuSCs remain quiescent state, but become proliferative differentiate into new injury. addition MuSCs, some interstitial progenitor (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, expressing PW1 negative for Pax7 (PICs), side population (SPCs), CD133-positive Twist2-positive have been identified playing direct indirect roles regenerating tissue. Here, we highlight heterogeneity, molecular markers, functional properties these explore role homeostasis, aging, muscle-related diseases. This review provides critical insights future therapies aimed at treating

Язык: Английский

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Nutritional Strategies for Muscle Atrophy: Current Evidence and Underlying Mechanisms

Molecular Nutrition & Food Research, Год журнала: 2024, Номер 68(10)

Опубликована: Май 1, 2024

Abstract Skeletal muscle can undergo detrimental changes in various diseases, leading to dysfunction and atrophy, thus severely affecting people's lives. Along with exercise, there is a growing interest the potential of nutritional support against atrophy. This review provides brief overview molecular mechanisms driving skeletal atrophy summarizes recent advances interventions for preventing treating The supplements include amino acids their derivatives (such as leucine, β‐hydroxy, β‐methylbutyrate, creatine), antioxidant (like Coenzyme Q10 mitoquinone, resveratrol, curcumin, quercetin, Omega 3 fatty acids), minerals magnesium selenium), vitamins vitamin B, C, D, E), well probiotics prebiotics Lactobacillus, Bifidobacterium, 1‐kestose). Furthermore, study discusses impact combined approach involving physical therapy prevent suggests appropriate multi‐nutritional multi‐modal based on individual conditions optimize treatment outcomes, enhances recovery function patients. By understanding behind implementing interventions, it possible enhance improve patients' quality life.

Язык: Английский

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(−)-Epigallocatechin-3-O-gallate or (−)-epicatechin enhances lipid catabolism and antioxidant defense in common carp (Cyprinus carpio L.) fed a high-fat diet: Mechanistic insights from the AMPK/Sirt1/PGC-1α signaling pathway

Aquaculture, Год журнала: 2024, Номер 587, С. 740876 - 740876

Опубликована: Март 27, 2024

Язык: Английский

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