Antioxidants最新文献

{"title":"Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.","authors":"Ying Wen, Pengfei Zhang, Xinyu Liao, Jiankang Liu, Yang Zhang, Xuyun Liu","doi":"10.3390/antiox15091134","DOIUrl":"10.3390/antiox15091134","url":null,"abstract":"<p><p>Preservation of mitochondrial integrity has emerged as a central hub in the anti-inflammatory effect of exercise. This narrative review advances a framework in which mitochondrial damage-associated molecular patterns (mtDAMPs) serve as the mechanistic bridge between exercise and inflammation. Mitochondrial dysfunction releases mtDAMPs, including mitochondrial DNA (mtDNA), reactive oxygen species, cardiolipin, N-formyl peptides, and ATP, which activate cGAS-STING, the NLRP3 inflammasome, TLR9, AIM2, ZBP1, and NF-κB signaling. Crosstalk among these pathways allows mild mitochondrial damage to escalate into chronic inflammation. Exercise opposes this cascade through the AMPK-PGC-1α axis, which coordinately activates four mitochondrial quality control (MQC) modules: biogenesis, antioxidant defense, dynamics, and mitophagy. The cardiovascular system illustrates this framework, as myocardial inflammation runs mainly through mtDNA-cGAS-STING signaling and vascular inflammation through oxidized mtDNA-NLRP3 signaling, while cardiovascular aging engages both axes at once. Throughout, exercise refers to repeated training rather than to a single bout, and the framework targets middle-aged and older adults with, or at risk of, cardiovascular disease. The upstream half of the sequence, in which training raises mitochondrial content and antioxidant capacity, rests on human muscle biopsy data; the downstream half remains largely preclinical. MQC is therefore proposed as a testable target rather than an established one.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons.","authors":"Pedro Amorim, Lívia de Sá Hayashide, Vitor Emanuel Leocadio, Mariana Marques, Isabelle Navarra, Cherley Borba Vieira Andrade, Jorge José de Carvalho, Rafael Serafim Pinto, Luan Pereira Diniz","doi":"10.3390/antiox15091127","DOIUrl":"10.3390/antiox15091127","url":null,"abstract":"<p><p>Astrocyte senescence is a recognized feature of brain aging, but its impact on neuronal mitochondrial homeostasis remains poorly defined, particularly in human cells. Here we show that doxorubicin-induced senescence disrupts mitochondrial function in primary human astrocytes and compromises their capacity to sustain neuronal bioenergetics. Senescent astrocytes accumulated a denser population of smaller, ultrastructurally damaged mitochondria together with increased levels of fission, fusion and biogenesis-associated proteins. Despite this apparent expansion of the mitochondrial compartment, these cells displayed reduced mitochondrial membrane potential, intracellular ATP and cellular metabolic activity, indicating accumulation of a functionally impaired mitochondrial population. Senescence also remodeled the extracellular mitochondrial compartment: conditioned medium from senescent astrocytes contained fewer mitochondrial particles with lower membrane potential and reduced ATP. Functionally, conditioned medium from control astrocytes increased TOMM20 and PGC-1α levels in human postmitotic neurons, whereas medium from senescent astrocytes failed to elicit this response and instead promoted hydrogen peroxide accumulation, ATP depletion and reduced cellular metabolic activity in the absence of overt cytotoxicity. Neurons acquired an astrocyte-derived MitoTracker signal from both conditions. Our data indicate that factors released by senescent human astrocytes are sufficient to induce neuronal mitochondrial and redox dysfunction.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NADES-Extracted SunGold Kiwifruit Polyphenols as Functional Ingredients in Antioxidant-Enriched Yoghurt.","authors":"Rifqah Azzahra Naulidia, Michelle Ji Yeon Yoo","doi":"10.3390/antiox15091126","DOIUrl":"10.3390/antiox15091126","url":null,"abstract":"<p><p>Natural deep eutectic solvents (NADES) offer a potentially food-compatible alternative for extracting plant polyphenols, although their direct application in yoghurt remains limited. This study evaluated the antioxidant and physicochemical properties of yoghurt fortified with SunGold kiwifruit extracts obtained using a selected choline chloride and glycerol NADES, with water extraction used for comparison. The phenolic profile of the NADES extract was characterised using LC-MS/MS. Both extracts were incorporated before (PRE) or after (POS) fermentation at concentrations of 10%, 20%, and 30% (<i>v</i>/<i>v</i>). The extracts and fortified yoghurts were analysed for total phenolic content (TPC), total flavonoid content (TFC), DPPH radical scavenging activity, FRAP, CUPRAC, and physicochemical properties. LC-MS/MS tentatively annotated several phenolic compounds in the NADES extract, with catechin showing the largest peak area among the annotated compounds. The water extract showed higher TPC and DPPH activity, whereas the NADES extract showed higher TFC, FRAP, and CUPRAC values. Increasing extract concentration generally increased the measured bioactive properties of the yoghurts, although the magnitude of change varied among assays and treatments. Water extract-fortified yoghurts generally showed higher TPC and DPPH values, while NADES extract-fortified yoghurts showed higher TFC, FRAP, and CUPRAC values. Extract type, fortification stage, and concentration also influenced pH, °Brix, viscosity, colour, and syneresis. Higher fortification concentrations reduced viscosity and increased syneresis, while low-concentration NADES extract-fortified yoghurts retained physicochemical properties closer to those of the control. Overall, the NADES extract showed potential as an ingredient for yoghurt fortification. Further studies are required to evaluate sensory acceptability, storage stability, starter culture viability, and gastrointestinal bioaccessibility.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Grade Endotoxemia Is Associated with NOX2-Mediated Oxidative Stress and Endothelial Dysfunction in Takotsubo Syndrome: A Cross-Sectional Study.","authors":"Lorenzo Loffredo, Enrico Maggio, Simona Bartimoccia, Vito Cantisani, Antonio Angeloni, Aurora Paraninfi, Paolo Ciacci, Simona Battaglia, Federica Armeli, Ilaria Maria Palumbo, Mariaelena Malvasi, Giancarlo D'Ambrosio, Pasquale Pignatelli, Roberto Carnevale, Francesco Violi, Francesco Barillà, Gaetano Tanzilli","doi":"10.3390/antiox15091124","DOIUrl":"10.3390/antiox15091124","url":null,"abstract":"<p><p>Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, may translocate from the gut into the bloodstream and increase oxidative stress through activation of NADPH oxidase 2 (NOX2), nitric oxide (NO) depletion and endothelial dysfunction. This study aimed to evaluate circulating LPS levels in TTS and investigate their association with NOX2 activation, oxidative stress, and endothelial dysfunction. Twenty consecutive patients with TTS and 20 age- and sex-matched healthy controls were included. Within 48 h of admission, fasting blood samples were collected to assess soluble NOX2-derived peptide (sNOX2-dp), hydrogen peroxide (H₂O₂), NO metabolites (NOx), LPS, and zonulin. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Compared with controls, TTS patients had significantly higher serum levels of sNOX2-dp, H₂O₂, LPS, and zonulin, lower NOx and impaired FMD. sNOX2-dp was positively correlated with LPS (Rs = 0.539, <i>p</i> < 0.001) and zonulin (Rs = 0.331, <i>p</i> = 0.037) and inversely correlated with FMD (Rs = -0.462, <i>p</i> = 0.003). NOx correlated negatively with H₂O₂, zonulin and LPS. In multivariable analysis, LPS was the only independent predictor of FMD (β = 0.498, SE = 0.126, <i>p</i> = 0.001) and sNOX2-dp (β = -0.572, SE = 0.034 <i>p</i> < 0.001); FMD (β = -0.347, SE = 0.455, <i>p</i> = 0.005), H₂O₂ (β = 0.445, SE = 0.155, <i>p</i> < 0.001), and zonulin (β = 0.298, SE = 2.309, <i>p</i> = 0.016) emerged as independent predictors of LPS (adjusted R² = 0.585). TTS is associated with low-grade endotoxemia, NOX2-driven oxidative stress, reduced NO bioavailability, and endothelial dysfunction. The independent association between LPS and NOX2 activation supports a potential gut-vascular axis in TTS pathophysiology.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinate Dehydrogenase Subunit D as a Redox-Responsive Mitochondrial Component Linked to Aquaporin-Associated Hydrogen Peroxide Signaling in Glioblastoma Cells.","authors":"Kuen-Jang Tsai, Kuan-Tso Chen, Chin-Chuan Tsai, Zi-Xuan Hong, Li-Ying Qiu, Chan-Chuan Liu, Kwang-Yu Chang, Pin-Yuan Chen, Chia-Hung Chien","doi":"10.3390/antiox15091125","DOIUrl":"10.3390/antiox15091125","url":null,"abstract":"<p><p>Glioblastoma (GBM) frequently recurs after temozolomide (TMZ) therapy and exhibits substantial redox plasticity. Our previous work showed that the effects of hydrogen peroxide (H₂O₂) vary with its level and between parental and TMZ-resistant GBM cells. Succinate dehydrogenase subunit D (SDHD), a membrane-anchoring component of mitochondrial complex II, is positioned at the interface of electron transport and redox homeostasis, but its regulation in GBM remains unclear. We therefore examined whether SDHD expression changes across distinct H₂O₂-responsive contexts involving aquaporins (AQPs) and AKT. TCGA transcriptomic analysis showed higher SDHD mRNA expression in WHO grade IV than in grade II/III gliomas, whereas paired primary/recurrent high-grade glioma samples showed heterogeneous SDHD changes at recurrence. TMZ reduced SDHD, and SDHD knockdown decreased intracellular reactive oxygen species. Combined redox perturbation reduced SDHD, whereas AKT inhibition restored SDHD expression. Under receptor-associated signaling conditions, EGFRvIII expression or CXCL12 stimulation increased measured H₂O₂ together with AQP3, AKT Ser473 phosphorylation, and SDHD. In TMZ-resistant cells, pharmacological perturbation of aquaporin-associated signaling decreased AQP9 together with AKT Ser473 phosphorylation and SDHD. An AQP3-targeting compound further reduced cell density when combined with TMZ. Together, these findings suggest that changes in SDHD expression are consistent with a compensatory redox response in GBM cells and that its regulation varies with the nature of H₂O₂-associated signaling during TMZ-related stress.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin Methacryloyl Hydrogel Encapsulating CiMECs-Derived Extracellular Vesicles Ameliorates Lactation Function via Alleviating Mammary Oxidative Stress.","authors":"Guodong Wang, Jiawen Duan, Longfei Sun, Tao Xu, Jianwei Chen, Aihao Xu, Quanhui Liu, Mengqin Qin, Shouyu Huo, Weiqing Li, Xiaozhen Li, Quanqing Zou, Prasanna Kallingappa, Dandan Zhang, Ben Huang","doi":"10.3390/antiox15091115","DOIUrl":"10.3390/antiox15091115","url":null,"abstract":"<p><p><b>Background</b>: Postpartum hypogalactia is a prevalent obstetric complication worldwide, closely associated with excessive oxidative stress and impaired antioxidant defense in mammary tissue. Current hormone-based therapies carry endocrine disruption risks, while natural antioxidant bioactive agents such as extracellular vesicles (EVs) are largely limited by rapid in vivo clearance and poor tissue retention. <b>Methods</b>: We constructed an injectable gelatin methacryloyl (GelMA) hydrogel system to encapsulate chemically induced mammary epithelial cell-derived EVs (CiMECs-EVs) and systematically evaluated their antioxidant and lactogenic activities via multi-omics analysis, cellular functional assays and a bromocriptine-induced murine hypogalactia model. <b>Results</b>: CiMECs-EVs induced a functional mammary epithelial-like phenotype in fibroblasts in a dose-dependent manner with functional cargo enriched in glutathione metabolism and redox-regulatory miRNAs. The GelMA matrix protected EV integrity and enabled sustained release, and the composite system significantly ameliorated mammary duct structure and lactation function in vivo with specific mammary tropism and no systemic toxicity, outperforming free EV treatment. <b>Conclusions</b>: This study presents a safe protein biomacromolecule-based antioxidant delivery platform that effectively restores mammary redox balance and antioxidant defenses, providing a promising non-hormonal therapeutic strategy for postpartum hypogalactia.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal Infection in Pregnancy Is Associated with Amniotic Oxidative Stress: Insights from AOPP and MDA on Neonatal Outcomes.","authors":"Meryem Kececi Oguzhanoglu, Icten Olgu Bafali, Kursat Oguzhanoglu, Senem Karacabey Cakmak, Busra Seker Atas, Muhammed Oguz Yildiz, Ali Cetin","doi":"10.3390/antiox15091123","DOIUrl":"10.3390/antiox15091123","url":null,"abstract":"<p><p>Amniotic oxidative stress in women with vaginal infection but no documented intra-amniotic infection has received little attention. In this prospective cohort study of 90 women undergoing elective cesarean delivery, 45 had symptomatic, culture- or Nugent-confirmed vaginal infection and 45 were asymptomatic controls. Amniotic fluid advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were measured by commercial ELISA. Both were higher in the infection group (median 7.96 versus 5.77 ng/mL and 12.49 versus 7.73 nmol/mL, both <i>p</i> < 0.001), with lower cord blood pH (<i>p</i> = 0.003) and more frequent neonatal intensive care unit (NICU) admission (26.7% versus 4.4%, <i>p</i> = 0.007). AOPP was associated with NICU admission (area under the curve 0.917, 95% CI 0.777 to 0.999), although this rests on 14 events with thresholds derived and evaluated in the same sample. Elevations were largest in the bacterial vaginosis and aerobic bacterial subgroups, but the etiologies did not differ. Both kits were designed for serum and are not validated for amniotic fluid, and 16.7% of MDA measurements fell outside the calibration range, so the MDA results are semi-quantitative. Vaginal infection at cesarean delivery is associated with higher amniotic oxidative stress markers; these findings are exploratory and require external validation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Histidine Derivatives-From Basic Research to Potential Applications in Cosmetics and Nutricosmetics.","authors":"Edyta Gołaś, Mateusz Maciejczyk","doi":"10.3390/antiox15091118","DOIUrl":"10.3390/antiox15091118","url":null,"abstract":"<p><p>Skin aging is a complex process influenced by oxidative stress, protein glycation, chronic inflammation, and increased extracellular matrix remodeling. Intensive research is underway on new anti-aging substances with multi-target mechanisms of action while maintaining safety and efficacy. Ergothioneine, selenoneine, and ovothiol A are natural histidine derivatives of marine origin, in which the oxygen atom of the hydroxyl group has been replaced with sulphur or selenium. In recent years, a broad spectrum of their biological activity has been demonstrated. Despite the well-documented antioxidant potential of these compounds, their anti-aging effects, particularly in terms of antiglycation and anti-inflammatory activity, remain insufficiently understood. This study presents the current state of knowledge regarding the biological activity of ergothioneine, selenoneine, and ovothiol A, and discusses available cosmetic preparations and dietary supplements containing these compounds. Meanwhile, significant research gaps have been identified regarding their potential use in the prevention and treatment of skin aging.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mung Bean Seed Coat Extract Promotes Diabetic Wound Healing in High-Glucose-Exposed HaCaT Keratinocytes.","authors":"Sineenad Teerapatpaisan, Alisa Naladta, Kamonpan Wanichsri, Penpimol Ponchunchoovong, Suthasinee Thapphasaraphong, Natsajee Nualkaew","doi":"10.3390/antiox15091119","DOIUrl":"10.3390/antiox15091119","url":null,"abstract":"<p><p>Mung bean seed coat (MBSC) is a byproduct of commercial vermicelli production that possesses essential activities capable of delaying diabetic wound progression. This study aimed to evaluate the potential of MBSC extracts to promote diabetic wound healing, an effect that has not yet been reported. The hypoglycemic effect was assessed by glucose uptake stimulation in L6 myotubes and by an α-glucosidase inhibition assay. Antiglycation was determined by BSA-glucose and BSA-methylglyoxal assays. Intracellular reactive oxygen species (ROS) reduction and wound healing were assessed in human keratinocytes (HaCaT) exposed to high glucose (HG), and gene expression in HG-wounded cells was analyzed by qPCR. The results demonstrated that the ethanolic extract (EE) from MBSC exhibited glucose-lowering effects and suppressed glycation reactions at the early and intermediate stages, with IC₅₀ values of 75 and 140 µg/mL, respectively. EE reduced ROS by 70%, stimulated cell proliferation by 57% in the high-glucose (HG)-exposed HaCaT cells, and accelerated cell migration to close the HG-exposed wound. EE increased the gene expression of Nrf2, NQO-1, SOD2, and CAT. It also downregulated TNF-α, upregulated TGF-β1, and downregulated MMP-9. In conclusion, EE has the potential to delay the progression of diabetic wounds by lowering blood glucose levels, inhibiting AGE and ROS formation, and enhancing cell proliferation and migration in HG-exposed HaCaT cells. The gene regulatory effects of EE were demonstrated as an Nrf2 activator that reduced oxidative stress, exerted anti-inflammatory effects, and regulated ECM balance. The preparation of oral and topical products could be further developed.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carnosine Potentiates a Compensatory Mitochondrial-Synaptic Proteomic Response in the ALS Cerebellum.","authors":"Hellen P Valerio, Valeria Oliveira, Stephanie Y Ferreira, Isabel R Pereira, Giuseppe Palmisano, Mariana P Massafera, Vanderson S Bispo, Fernanda M Prado, Paolo Di Mascio, Marisa H G Medeiros","doi":"10.3390/antiox15091117","DOIUrl":"10.3390/antiox15091117","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and chronic neuroinflammation in the brain and spinal cord, involving complex interactions between neurons and immune cells. Carnosine (β-alanyl-L-histidine) has pathophysiological relevance due to its ability to detoxify reactive carbonyl species, including α,β-unsaturated aldehydes, scavenge free radicals, and chelate zinc, and has also been proposed to function in the central nervous system as a histidine reservoir for histamine synthesis. Here, we investigated the effects of carnosine supplementation on the cerebellar proteome of SOD1^G93A ALS rats using quantitative proteomics. Carnosine treatment extensively remodeled mitochondrial, antioxidant, and synaptic vesicle-trafficking protein networks and increased the abundance of glutamatergic and GABAergic receptor subunits relative to untreated ALS animals, with several of these changes exceeding wild-type levels. Pathway enrichment analyses identified significant up-regulation of Rab-mediated vesicle trafficking, synaptic vesicle cycling, and neurotransmitter transport/secretion pathways, alongside a partial reduction in RNA splicing and proteasomal subunits that were elevated in untreated ALS animals. Cross-comparison with the ALS-associated proteomic signature revealed that most carnosine-responsive proteins followed, rather than reversed, the direction of disease-associated change, indicating that carnosine predominantly potentiates an endogenous compensatory program rather than restoring a wild-type-like proteome. Collectively, these findings show that carnosine drives systems-level remodeling of mitochondrial and synaptic networks in the ALS cerebellum, identifying candidate compensatory pathways and supporting further functional validation of carnosine as a component of multimodal therapeutic strategies in ALS.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"15 9","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13603265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}