Protein and Peptide Letters最新文献

{"title":"Targeting α-Synuclein: Current Strategies and Emerging Therapies for Synucleinopathies.","authors":"Vidhan Chand Bala, Mukesh Kumar Singh, Amit Kumar, Sunil Kumar Tiwari, Asheesh Kumar Gupta, Rakesh Chawla, Sushil Kumar","doi":"10.2174/0109298665429866260217115717","DOIUrl":"10.2174/0109298665429866260217115717","url":null,"abstract":"<p><p>Alpha-synuclein (α-syn) is a crucial protein involved in the pathogenesis of Parkinson's Disease (PD) and other synucleinopathies. It is important with respect to neuron health, regulation of α-syn protein synthesis, and its degradation. Numerous cellular pathways implicated in the process of autophagy, chaperone, and proteolysis play a vital role in the maintenance of α-syn protein homeostasis. Autophagy dysfunction defeats α-syn protein accumulation and neuroinflammation, as present in dementia with Lewy bodies and sporadic PD. Oxidative stress is another key factor that intensifies α-syn protein misfolding and aggregation, thereby leading to neurodegeneration. Involvement in the treatment of α-syn related disorders includes passive and active immunization, inhibitors of protein aggregation, gene silencing technology, modulators of synaptic function, and target drug delivery systems. Other α-syn related therapy approaches include the development of a novel herbal formulation focusing on the gut-brain axis and interventions designed to enhance protein quality control. As clinical trials move forward, minimizing challenges related to the target involved, biomarkers, and patient stratification is crucial to decoding these therapies into effective management. These insights not only advance our understanding of α-syn biology but also highlight the urgency of early and multi-targeted therapeutic interventions.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"258-274"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Activity of a Defensin-Rich Fraction from <i>Capsicum chinense</i> Fruits: Insights for Biotechnological Applications against Fungal Infections.","authors":"Mariana C L Aguieiras, Erica O Mello, Larissa M Resende, Gabriel B Taveira, Thayna A M Souza, Milena B Cherene, Arielle P B F Oliveira, Celso S Nagano, Renata P Chaves, Andre O Carvalho, Rosana Rodrigues, Fernanda Trindade, Maura Da Cunha, Valdirene M Gomes","doi":"10.2174/0109298665377738250626233111","DOIUrl":"10.2174/0109298665377738250626233111","url":null,"abstract":"<p><strong>Background: </strong>The increasing resistance of fungal pathogens to conventional antifungal treatments has led to a global rise in fungal infections, affecting human health (Candida spp.) and agricultural productivity (Colletotrichum and Fusarium spp.). Antimicrobial peptides (AMPs), such as defensins, have gained attention for their potential in controlling these infections due to their broad-spectrum activity.</p><p><strong>Objectives: </strong>The aim of this study was to partially purify and characterize the antifungal activity of a defensin-enriched fraction (F3) from Capsicum chinense fruits. Specifically, we sought to evaluate its efficacy against pathogenic fungi and yeasts, and to assess the relative abundance of defensins in the fraction.</p><p><strong>Methods: </strong>The F3 fraction was obtained using ion exchange and molecular exclusion chromatography. Reverse-phase chromatography (HPLC) was then employed for further purification. The antifungal activity of F3 was tested against Colletotrichum, Fusarium, and Candida species. Mass spectrometry was used to identify and characterize the defensin (CcDef3) within the fraction. The presence of the defensin relative to other components was inferred from electrophoretic profiles and peptide analysis.</p><p><strong>Results: </strong>The F3 fraction exhibited significant antifungal activity, with growth inhibition of Colletotrichum lindemuthianum of 51% and 60.9% at concentrations of 100 and 200 μg mL-1, respectively. The fraction also inhibited the growth of several Candida species, notably C. nivariensis (93.8%) and C. bracarensis (79.6%) at 100 μg mL-1. Cell viability analysis indicated a fungistatic effect. Fluorescence microscopy assays showed that F3 induced membrane permeabilization in C. parapsilosis and C. lindemuthianum, and increased ROS production in C. pelliculosa and F. solani. The defensin-rich H8 fraction, containing a 6.5 kDa protein (CcDef3), was identified as a major component via mass spectrometry.</p><p><strong>Discussion: </strong>The ongoing development of resistance in fungal strains, particularly Candida species, against traditional antibiotics and antifungals has turned into a significant medical concern and has increased the need for new treatment options.</p><p><strong>Conclusion: </strong>These results suggest that the F3 fraction, particularly the defensin CcDef3, has potential as an antifungal agent for biotechnological and therapeutic applications. However, further studies are needed to quantify the contribution of CcDef3 relative to other components in the fraction and to fully isolate the defensin for in-depth analysis.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"49-62"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction to: Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular-structure Adjuvant Activity for Antibody Specificity Enhancement.","authors":"Brenda Molina-Ramírez, Nidia Cabral-Hipólito, Irais Castillo-Maldonado, Dealmy Delgadillo-Guzmán, Rocío Meza-Velázquez, Agustina Ramírez-Moreno, Erika Flores-Loyola, Pablo Ruíz-Flores, Jorge Haro-Santa Cruz, Perla-Karina Espino-Silva, Joaquín Avalos-Soto, Miguel-Ángel Téllez-López, Rubén Daniel Arellano Pérez Vertti, Manuel-Gerardo Rosales-González, David Pedroza-Escobar","doi":"10.2174/092986653302260507094257","DOIUrl":"https://doi.org/10.2174/092986653302260507094257","url":null,"abstract":"<p><p>The article entitled \"Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular- Structure Adjuvant Activity for Antibody Specificity Enhancement,\" published in the journal, Protein and Peptide Letters, Volume 29, Issue 11 (2022) (DOI: 10.2174/0929866529666220902152147), has been retracted by the publisher. This decision follows a thorough investigation that identified inconsistencies in the reported work, along with directives received from the authors' institution. In light of these concerns, the integrity and reliability of the data presented in the article can no longer be assured. Therefore, the findings of this study should not be cited or relied upon as a scientific reference. This retraction has been made in agreement with the Editor-in-Chief. The publisher regrets any inconvenience caused to readers and the scientific community. The Bentham Editorial Policy on Retraction is available at https://benthamscience.com/editorial-policies-main.php.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 2","pages":"497"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-Wide Acetylome Profiling Suggests Extensive Aspirin-Driven Remodeling of Networks Relevant to THP-1 Macrophage Differentiation","authors":"Zi-Hui Ma, Yuan-Qing Pan, Pir Tariq Shah, Li Xing","doi":"10.2174/0109298665444488260123052552","DOIUrl":"10.2174/0109298665444488260123052552","url":null,"abstract":"<p><strong>Introduction: </strong>Acetylsalicylic Acid (aspirin or ASA) is known to exhibit immunomodulatory effects not only through Cyclooxygenase (COX) inhibition but also through direct protein acetylation. However, its impact on innate immune cell differentiation remains unclear.</p><p><strong>Materials and methods: </strong>To fill this gap, the study used quantitative acetyl-proteomics to track changes in the lysine acetylome during THP-1 monocyte differentiation into macrophages following ASA preconditioning.</p><p><strong>Results: </strong>Our results showed that preconditioning of THP-1 macrophages with 300 μg/ml ASA for 3 hours before differentiation induced persistent acetylation changes. We identified 5,199 differentially acetylated sites across 2,678 proteins, with 2,595 sites upregulated and 2,604 downregulated. The sequence analysis revealed a strong preference of ASA for acidic residues like E_K motifs and hydrophobic regions. The subcellular localization analysis showed notable enrichment in the nucleus (1,166 proteins), cytoplasm (850 proteins), and mitochondria (405 proteins), and frequently contained functional domains like PWWP, SET, RhoGEF, and RNA recognition motifs.</p><p><strong>Discussion: </strong>The Gene Ontology analysis linked these proteins to cellular metabolism, regulation, and stimulus response, while our KEGG analysis connected them to neurodegeneration, infection, and metabolic pathways. Furthermore, the protein-protein interaction networks further showed coordinated changes in ribosomal, signaling, and chromatin complexes.</p><p><strong>Conclusion: </strong>The findings show that ASA preconditioning leaves a lasting acetylome signature during macrophage differentiation reprogramming regulatory networks relevant to macrophage differentiation and functional networks via motif-directed acetylation. The results provide a plausible COX-independent model in which structural motif-targeted acetylation may underlie ASA’s immunomodulatory role.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"319-363"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Nature of Venom: Transforming Toxins into Therapeutic Peptides.","authors":"Chloe Zi En Wong, Wei Hsum Yap, Adeline Yoke Yin Chia, Yin Quan Tang","doi":"10.2174/0109298665429958251204082928","DOIUrl":"10.2174/0109298665429958251204082928","url":null,"abstract":"<p><p>Venom has been extracted from venomous animals since ancient times for use as hunting tools or biological weapons. In the modern era, the focus has shifted toward the biomedical potential of venom, particularly its rich composition of bioactive compounds. Among these, venom peptides are of particular interest due to their potent and selective biological activities. These peptides often constitute a significant portion of crude venom mixtures and have emerged as promising candidates for drug development. The growing body of research in this field has led to the establishment of \"venomics,\" a discipline that integrates proteomics, transcriptomics, and genomics to comprehensively characterize venom components. Technological advancements, such as high-throughput sequencing, mass spectrometry, and advanced computational tools, have revolutionized venomics, enabling deeper insights into venom composition, function, and evolutionary biology. These innovations have facilitated the discovery of venom-derived peptides with therapeutic applications, including treatments for chronic pain, cancer, cardiovascular diseases, and autoimmune disorders. However, despite these promising developments, challenges remain. These include the complexity of venom mixtures, ethical considerations in venom collection, and difficulties in translating in vitro findings into clinical applications. This review explores the evolution and technological progress of venomics, highlights key therapeutic applications of venom peptides, and discusses current limitations and future prospects in the field.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"98-116"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Autoimmunity in Myasthenia Gravis: From Conventional to Novel Therapeutic Approaches.","authors":"Vishal Chanalia, Smita Narwal, Gurvirender Singh, Dushyant, Ashwani K Dhingra, Nisha Grewal, Khushbu, Ashutosh","doi":"10.2174/0109298665429857260206223221","DOIUrl":"10.2174/0109298665429857260206223221","url":null,"abstract":"<p><p>Myasthenia Gravis is a chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness, most commonly involving ocular, bulbar, respiratory, and limb muscles. This weakness stems from autoantibodies, predominantly immunoglobulin G, against neuromuscular junction components such as acetylcholine receptors or muscle-specific kinase, which ultimately reduces synaptic transmission. MG causes a severe functional impact on normal patients, which often contributes to the reduced quality of life and life-threatening myasthenic crises. This article provides an extensive review of MG's immunopathogenesis with a focus on T and B lymphocytes, pro-inflammatory cytokine involvement, and the components of the complement cascade. Humoral and innate immune mechanisms cooperate and indirectly result from antibodies and continued neuromuscular dysfunction. Clinical MG approval usually depends on a combination of a clinical approach to testing antibodies, electrophysiological technique trials, and, if necessary, imaging methods for thymoma or thymic fusion abnormalities. Regular MG treatment involves acetylcholinesterase inhibitors, corticosteroids, and steroid-sparing immunosuppressant agents (e.g., azathioprine, mycophenolate mofetil). Rapid treatment of MG exacerbations necessitates a process of rapid immunomodulation, including plasma exchanges and intravenous immunoglobulin to rapidly reduce reversed autoantibodies. Novel drug discovery is aimed at targeted immunomodulation, including clinical application of inhibitors of the complement C5 (eculizumab, ravulizumab, zilucoplan), type I neonatal Fc receptor antagonists (efgartigimod, rozanolixizumab), BTK inhibitors, B-cell-directed monoclonal antibodies, and new dendritic cell T cell antireceptor constructs. They can carve out paradigm shifts as these novel resourcing solutions and therapeutic options allow precision medicine to individual immunopathogenic profiles. Synergistic combinations of conventional and modern medicine are a promising comprehensive strategy for MG patients. Reappraisal driven by the biological mechanism, three may deliver better long-term functional outcomes and quality of life.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"155-175"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimerization of SARS-CoV-2 3CLpro and the Role of the A7G/V125G Zipper Interface.","authors":"Rafida Razali, Cahyo Budiman, Vijay Kumar","doi":"10.2174/0109298665442327260216063524","DOIUrl":"10.2174/0109298665442327260216063524","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>The 3-chymotrypsin-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for viral replication and is catalytically active only in its dimeric form. Elucidating the molecular determinants that stabilize this dimer may uncover novel antiviral drug targets. This study aimed to characterize the oligomerization behavior of wild-type 3CLpro and to elucidate the functional role of an alanine- valine zipper motif in dimer stability and enzymatic activity.</p><p><strong>Methods: </strong>Wild-type 3CLpro (3CLpro-WT) was heterologously expressed in Escherichia coli BL21(DE3) and purified by nickel-affinity chromatography. Oligomerization behavior was examined using Size-Exclusion Chromatography (SEC) under varying protein concentrations, pH conditions, and ionic strengths. An alanine-valine zipper mutant (A7G/V125G; 3CLpro-ZM) was generated by site-directed mutagenesis, overexpressed, purified using the same protocol, and analyzed for changes in folding, oligomerization, and enzymatic activity.</p><p><strong>Results: </strong>3CLpro-WT predominantly existed as a stable dimer, independent of protein concentration and ionic strength, but was destabilized under extreme pH conditions. In contrast, 3CLpro-ZM exhibited a perturbed dimerization equilibrium, altered secondary structure, and a pronounced reduction in both protease and esterase activities compared with the wild-type enzyme.</p><p><strong>Discussion: </strong>These findings demonstrate that hydrophobic interactions are the primary force stabilizing the 3CLpro dimer, while ionic interactions provide pH-sensitive modulation. Disruption of the alanine-valine zipper compromises dimer integrity and allosterically impairs catalytic activity, despite the mutation being distant from the active site.</p><p><strong>Conclusion: </strong>The Ala7-Val125 interface contributes to 3CLpro stability and activity and may be a promising site for future allosteric inhibitor design.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"379-393"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocompatible Excipients from Microalgae: Advancing Protein and Peptide Therapeutics through Sustainable Formulation Strategies.","authors":"Shikha Baghel Chauhan, Indu Singh, Aniket Yadav, Chirag Jain","doi":"10.2174/0109298665413424251128131420","DOIUrl":"10.2174/0109298665413424251128131420","url":null,"abstract":"<p><p>As a distinctive and sustainable raw material for pharmaceutical excipients, microalgae have emerged as a significant source of biopolymer compounds with immense functional and medicinal value. The pharmacoeconomic importance of key biopolymer compounds isolated from microalgae, such as fucoidan, ulvan, laminarin, and paramylon, having mucoadhesive, bioactive, and controlled release properties that meet the standards of advanced drug delivery systems, has been discussed in this review. Due to the compact cultivation requirements of microalgae that fix significant quantities of carbon dioxide from the environment, biopolymer compounds play an important role in the development of ecologically sustainable production practices. Also critically evaluated in this investigation are the advantages and limitations of industrial-scale cultivation practices of microalgae, which include closed bioreactor cultivation and open-pond cultivation procedures, for biopolymer applications. This study also discusses industrial applications that currently hinder the application of biopolymer compounds of microalgae to the pharmaceutical industry. Moreover, the ability of such compounds to be applied in formulation science has been underscored by their multifaceted properties, from thickening, gelation, and film-forming to immunomodulatory and antioxidant properties. The increased adoption of safer and more ecofriendly alternatives by the pharmaceutical industry to replace synthetic excipients has been facilitated by such compounds' ability to either complement or replace them. In order to incorporate microalgae-derived excipients into future pharmaceutical formulations, research on such compounds has been underscored as needed.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"244-257"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunity in Harmony: Utilizing Overlapping Epitopes for Tuberculosis and COVID-19 Protection.","authors":"Kritika Pasricha, Shivank Prajapati, Taruna Lamba, Jonaid Ahmad Malik, Mohd Affan Khan, Sidhanta Nanda, Mohammad Adeel Zafar, Nitesh Mani Tripathi, Anupam Bandyopadhyay, Javed Naim Agrewala","doi":"10.2174/0109298665417756251207111117","DOIUrl":"10.2174/0109298665417756251207111117","url":null,"abstract":"<p><strong>Introduction: </strong>The BCG vaccine, widely administered against tuberculosis, has also been linked to reduced incidence of bacterial and viral infections, particularly those affecting the respiratory tract. Its antigens enhance innate immune responses and contribute to therapeutic effects, such as those observed in bladder cancer. Notably, reduced COVID-19 incidence has been reported in BCG-vaccinated populations from TB-endemic regions.</p><p><strong>Methods: </strong>To investigate this hypothesis, immunoinformatics tools were employed to identify overlapping CD4, CD8, and B-cell epitopes shared between Mycobacteria and SARS-CoV-2. The most promising CD8 epitope was synthesized using the SPPS-Fmoc method, and antigen-specific Tcell proliferation was evaluated by CFSE dye-dilution assay. Additionally, the expression of proand anti-inflammatory molecules was assessed using qRT-PCR.</p><p><strong>Results: </strong>Multiple overlapping T-cell and B-cell epitopes were identified between Mycobacteria and SARS-CoV-2. The T-cell epitopes displayed promiscuous binding characteristics, high immunogenicity, and strong affinity for both HLA class I and class II alleles. Experimental validation using the most immunodominant T-cell epitope confirmed its ability to induce proliferation and differentiation of T cells isolated from COVID-19-vaccinated individuals.</p><p><strong>Discussion: </strong>The overlapping T-cell and B-cell epitopes identified through this approach may provide broader and more robust protection than initial exposure to virus-specific antigens, which the immune system encounters for the first time during infection or vaccination. This strategy may therefore support the rapid and effective development of future vaccines, particularly against emerging pathogens.</p><p><strong>Conclusion: </strong>The findings suggest that the higher level of protection observed in TB-endemic countries during recent pandemics may be attributable to cross-reactive mycobacterial antigens that stimulate protective immunity.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"290-308"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOTS-c Protects Against Acetaminophen-induced Liver Injury through the MAPK Signaling Pathway.","authors":"Nan Li, Yimin Xu, Qixin Chen, Jinhong Jiang, Wei Wei Li","doi":"10.2174/0109298665430028251230103831","DOIUrl":"10.2174/0109298665430028251230103831","url":null,"abstract":"<p><strong>Objective: </strong>Acetaminophen (APAP)-induced liver injury (AILI) is a leading cause of acute liver failure worldwide, but effective therapeutic strategies are still lacking. MOTS-c, a mitochondrial-derived peptide, has demonstrated hepatoprotective properties in models of nonalcoholic steatohepatitis (NASH) and hepatitis B virus (HBV) infection. This study aims to explore the role and underlying mechanisms of MOTS-c in AILI.</p><p><strong>Methods: </strong>An AILI model was established in male C57BL/6 mice via intraperitoneal (i.p.) injection of APAP (300 mg/kg). The therapeutic potential of MOTS-c and its mechanisms were assessed using behavioral tests, qPCR, western blotting, ELISA, immunohistochemistry, immunofluorescence, and TUNEL staining.</p><p><strong>Results: </strong>MOTS-c levels in both plasma and liver tissues were significantly reduced in APAPinduced AILI mice compared with controls. Administration of MOTS-c via i.p. injection markedly attenuated APAP-induced increases in AST and ALT levels, histopathological liver damage, and other liver injury markers. MOTS-c treatment suppressed the release of pro-inflammatory factors (TNF-α, IL-1β, IL-6, and COX-2) and macrophage infiltration induced by APAP. Furthermore, MOTS-c treatment significantly restored GSH content, diminished reactive oxygen species (ROS) production, and oxidative stress. TUNEL staining confirmed that increased apoptosis in APAPtreated livers was significantly attenuated by MOTS-c, which are key contributors to hepatocyte death and liver injury. Mechanistic studies revealed that MOTS-c inhibited APAP-induced phosphorylation of MAPK pathway components, including ERK, JNK, and p38. The protective effects of MOTS-c on serum ALT and AST levels were abolished by co-treatment with inhibitors of ERK, JNK, and p38.</p><p><strong>Discussion: </strong>This study reveals that the mitochondrial peptide MOTS-c can alleviate drug-induced liver injury by suppressing oxidative stress and inflammation via the MAPK pathway. This positions MOTS-c as a promising therapeutic candidate for treating APAP-induced liver injury.</p><p><strong>Conclusion: </strong>This study demonstrates that administering MOTS-c effectively protects against APAP-induced liver injury in mice. The protective mechanism involves suppressing the damaging MAPK signaling pathway (ERK, JNK, p38), which in turn reduces oxidative stress, inflammation, and cell death.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"309-324"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}