Current protein & peptide science最新文献

{"title":"How Useful are Antimicrobial Peptide Properties for Predicting Activity, Selectivity, and Potency?","authors":"Brandt Bertrand, Pablo Luis Hernandez-Adame, Carlos Munoz-Garay","doi":"10.2174/0113892037317887240625054710","DOIUrl":"10.2174/0113892037317887240625054710","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are recognized for their potential application as new generation antibiotics, however, up to date, they have not been widely commercialized as expected. Although current bioinformatics tools can predict antimicrobial activity based on only amino acid sequences with astounding accuracy, peptide selectivity and potency are not foreseeable. This, in turn, creates a bottleneck not only in the discovery and isolation of promising candidates but, most importantly, in the design and development of novel synthetic peptides. In this paper, we discuss the challenges faced when trying to predict peptide selectivity and potency, based on peptide sequence, structure and relevant biophysical properties such as length, net charge and hydrophobicity. Here, pore-forming alpha-helical antimicrobial peptides family isolated from anurans was used as the case study. Our findings revealed no congruent relationship between the predicted peptide properties and reported microbial assay data, such as minimum inhibitory concentrations against microorganisms and hemolysis. In many instances, the peptides with the best physicochemical properties performed poorly against microbial strains. In some cases, the predicted properties were so similar that differences in activity amongst peptides of the same family could not be projected. Our general conclusion is that antimicrobial peptides of interest must be carefully examined since there is no universal strategy for accurately predicting their behavior.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"22-40"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632930","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":"Preliminary Analysis of Potentially Overlapping Differentially Expressed Proteins in Both the Spinal Cord and Brain of SOD1 G93A Mice.","authors":"Shi-Shi Jiang, Hong-Bing Nie, Shan Hua, Meng Xie, Ren-Shi Xu","doi":"10.2174/0113892037293525240621120033","DOIUrl":"10.2174/0113892037293525240621120033","url":null,"abstract":"<p><strong>Objective: </strong>Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS).</p><p><strong>Methods: </strong>Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation.</p><p><strong>Results: </strong>Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival.</p><p><strong>Conclusion: </strong>This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"57-75"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562904","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":"Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0113892037326839241014054430","DOIUrl":"10.2174/0113892037326839241014054430","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the most common kind of dementia worldwide, is characterized by elevated levels of the amyloid-β (Aβ) peptide and hyperphosphorylated tau protein in the neurons. The complexity of AD makes the development of treatments infamously challenging. Apolipoprotein E (APOE) genes's ε4 allele is one of the main genetic risk factors for AD. While the APOE gene's ε4 allele considerably increases the chance of developing AD, the ε2 allele is protective compared to the prevalent ε3 variant. It is fiercely discussed how APOE affects the development and course of disease since it has a variety of activities that influence both neuronal and non-neuronal cells. ApoE4 contributes to the formation of tau tangles, deposition of Aβ, neuroinflammation, and other processes. Four decades of research have provided a significant understanding of the structure of APOE and how this may affect the neuropathology and pathogenesis of AD. APOE is a crucial lipid transporter essential for the growth of the central nervous system (CNS), upkeep, and repair. The mechanisms by which APOE contributes to the pathophysiology of AD are still up for discussion, though. Evidence suggests that APOE affects the brain's clearance and deposition of Aβ. Additionally, APOE has Aβ-independent pathways in AD, which has led to the identification of new functions for APOE, including mitochondrial dysfunction. This study summarizes important studies that describe how APOE4 affects well-known AD pathologies, including tau pathology, Aβ, neuroinflammation, and dysfunction of neural networks. This study also envisions some of the therapeutic approaches being used to target APOE4 in the hopes of preventing or treating AD.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"259-281"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892118","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":"Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.","authors":"Zhongcheng Xie, Qin Hou, Yinling He, Yushu Xie, Qinger Mo, Ziyi Wang, Ziye Zhao, Xi Chen, Tianhong Peng, Liang Li, Wei Xie","doi":"10.2174/0113892037315874240826112422","DOIUrl":"10.2174/0113892037315874240826112422","url":null,"abstract":"<p><p>Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"89-104"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119202","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":"Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures.","authors":"Komal Gupta, Vikram Sharma, Tohfa Siddiqui","doi":"10.2174/0113892037336137250102104842","DOIUrl":"10.2174/0113892037336137250102104842","url":null,"abstract":"<p><p>In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes. In pharmaceuticals, gene therapy holds immense potential for addressing genetic disorders, offering a personalized approach to medicine. Immunotherapy, on the other hand, harnesses the body's immune system to combat diseases, including tumors, by enhancing immune responses or directly targeting malignant cells. RNA-based therapeutics have gained prominence due to their ability to modulate gene expression, offering targeted and precise interventions for a wide range of diseases. Cell-based therapies involve the transplantation or manipulation of cells to restore or enhance their function, offering innovative solutions for diseases such as neurodegenerative disorders and cardiovascular diseases. Furthermore, targeted tumor therapies have revolutionized tumor cure by specifically targeting molecular alterations driving tumor growth and minimizing damage to healthy cells. Overall, these novel therapeutic approaches represent a paradigm shift in medicine, offering tailored and precise interventions with the potential to significantly improve patient outcomes and quality of life.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"436-450"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058334","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":"Purification, Characterization, and Antimicrobial Activity Against <i>Candida parapsilosis</i> and <i>Staphylococcus aureus</i> of a Highly Stable Type-1 Cystatin from Terminalia catappa L. Seeds.","authors":"Amanda M A Moura, Jose Tadeu A Oliveira, Daniele O B Sousa, Lucas P Dias, Nadine M S Araujo, Raquel de O Rocha, Tawanny K B Aguiar, Joao M M Neto, Viviane O Silva, Ricardo M Feitosa, Queilane L S G Chaves, Marcio V Ramos, Cleverson D T Freitas","doi":"10.2174/0113892037339021241017084509","DOIUrl":"10.2174/0113892037339021241017084509","url":null,"abstract":"<p><strong>Introduction: </strong>Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant.</p><p><strong>Methods: </strong>The current study purified, characterized, and assessed the antimicrobial activity of a papain inhibitor from <i>Terminalia catappa</i> L. seeds.</p><p><strong>Results: </strong>The inhibitor was purified by heating the crude extract at 80°C for 30 min, followed by ion exchange chromatography on a DEAE cellulose column. The purification index was 9-fold, yielding 2.3%. SDS-PAGE and size exclusion chromatography revealed that the protease inhibitor (<i>Tc</i>PI) is a 15.9 kDa monomeric protein. The inhibition kinetics showed that <i>Tc</i>PI is a competitive inhibitor specific to papain (Ki = 1.02 x 10^-4 M). <i>Tc</i>PI remained active even after heating at 100oC for 120 min and at pH conditions varying from 2.0 to 10.0. Even after 60 min, <i>Tc</i>PI was resistant to papain proteolysis. <i>Tc</i>PI exhibited antimicrobial activity against <i>Candida parapsilosis</i> and <i>Staphylococcus aureus.</i> Conclusion: Here, we show that <i>Tc</i>PI is a highly stable type-1 cystatin with the potential to combat infections caused by <i>C. parapsilosis</i> and <i>S. aureus</i>. Additional investigations into <i>Tc</i>PI's structural aspects and mechanism of action, as well as safety assessments, are essential prerequisites for its potential application as a novel therapeutic intervention.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"308-319"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892820","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":"Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10.","authors":"Hakan Alici, Vladimir N Uversky, David E Kang, Junga Alexa Woo, Orkid Coskuner-Weber","doi":"10.2174/0113892037335036241007043530","DOIUrl":"10.2174/0113892037335036241007043530","url":null,"abstract":"<p><strong>Introduction: </strong>The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10^Q108P proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.</p><p><strong>Methods: </strong>This study presents the foundational characterization of the structural features of CHCHD10^Q108P and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.</p><p><strong>Results: </strong>Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.</p><p><strong>Conclusion: </strong>The reported structural properties hold promise for informing the development of more effective treatments for ALS.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"201-212"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496660","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 Role of Sirtuins in Diabetic Nephropathy: A Comprehensive Review.","authors":"Pranay Wal, Tarannum Tarannum, Lalji Baldaniya, Kiranjeet Kaur, Priyanka Singh, Namra Aziz, Komal Singh, Amin Gasmi","doi":"10.2174/0113892037340795241202044932","DOIUrl":"10.2174/0113892037340795241202044932","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy is characterized by elevated oxidative stress and chronic inflammation in the kidneys. A class of proteins called sirtuins is well-known to be important for a number of cellular functions, such as metabolism, stress tolerance, and ageing. Among them, SIRT1 is associated with the progression of diabetic nephropathy, a dangerous kidney-related consequence of diabetes mellitus. Thus, this study aims to examine the function and pathways of sirtuin that are responsible for the progression of this disease.</p><p><strong>Methods: </strong>Publications considered from the standard databases like Pubmed-Medline, Google Scholar, and Scopus using standard keywords, \"Sirtuin,\" Signalling pathway\", and \"Diabetic Nephropathy\" well described the actual knowledge on the scientific literature indicating patient susceptibility to kidney disease that is influenced by sirtuin-1 gene variants.</p><p><strong>Results: </strong>The research results imply that sirtuins offer enormous promise as cutting-edge therapeutic targets for kidney disease prevention and management. Renal fibrosis, metabolic disorders, renal impairment, and a possible regulation mechanism all probably entail blocking inflammation through various signalling pathways.</p><p><strong>Conclusion: </strong>A comprehensive understanding of the fundamental pathophysiological pathways targeting sirtuin is essential as a diagnostic tool. For the treatment of diabetic nephropathy, researchers are developing therapeutic techniques to target biological roles and functions of different types of sirtuin, processes, and signalling pathways.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"407-421"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022609","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":"Insight of Intestinal Fatty Acid Binding Protein as a Potential Biomarker in the Biology of Epithelial Damage of Gastrointestinal Membrane.","authors":"Nahid Rehman, Anjana Pandey","doi":"10.2174/0113892037311290240930054913","DOIUrl":"10.2174/0113892037311290240930054913","url":null,"abstract":"<p><p>The diagnosis of intestinal injury remains a challenge as it is rare in occurrence and transpires in multiple traumatized patients. The deferred finding of injury of intestines upsurges multiple risks such as septicemia, numerous organ failures as well as mortality. In this review, we corroborate with the goals of proposing surrogate biomarkers that consent to the measurement of the permeability of intestines more effortlessly. The expression of intestinal fatty acid binding protein (I-FABP) is exclusive in the intestine and has been reported to release extracellularly upon damage caused to tissues. This work focuses on evaluating the legitimacy of I-FABP as an initial biomarker to distinguish abdominal damage predominantly from an injury to the intestine.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"321-333"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926721","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":"Comparative Proteomic Analysis of Cell Wall Proteins of Aminoglycosides Resistant and Sensitive <i>Mycobacterium tuberculosis</i> Clinical Isolates.","authors":"Devesh Sharma, Sakshi Gautam, Nalini Srivastava, Abdul Mabood Khan, Deepa Bisht","doi":"10.2174/0113892037334796240927055243","DOIUrl":"10.2174/0113892037334796240927055243","url":null,"abstract":"<p><strong>Introduction: </strong>The rising prevalence of <i>Mycobacterium tuberculosis (M.tb)</i> strains resistant to aminoglycosides (amikacin and kanamycin) challenges effective TB control and treatment. Understanding the mechanisms behind this resistance is crucial since aminoglycosides are a mainstay of TB therapy.</p><p><strong>Aim: </strong>The study aimed to analyze the cell wall proteins overexpressed in aminoglycosides-resistant isolates of <i>Mycobacterium tuberculosis</i> using proteomics approaches.</p><p><strong>Methods: </strong>We used two-dimensional electrophoresis and mass spectrometry to compare the cell wall proteomes of aminoglycosides-resistant and susceptible clinical isolates. The overexpressed protein spots were excised and identified using liquid chromatography-mass spectrometry (LC/MS). The identified proteins were subsequently analyzed for molecular docking, pupylation site identification, and STRING analysis.</p><p><strong>Results: </strong>We found a total of nine significantly upregulated proteins in aminoglycosides-resistant isolates. Three of these proteins were the same (isoform), resulting in the identification of seven unique proteins. Specifically, Rv3841 and Rv1308 belonged to intermediary metabolism and respiration; Rv2115c to the cell wall and cell processes; Rv2501c, Rv2247 and Rv0295c to lipid metabolism; and Rv2416c to virulence, detoxification/adaptation. Notably, variations in these proteins support cell wall integrity, aiding mycobacteria's establishment and proliferation. Molecular docking study revealed that both drugs bind strongly to the proteins' active site regions. Additionally, the GPS-PUP algorithm successfully identified possible pupylation sites within these proteins, except Rv0295c. Based on interactome analysis using the STRING 12.0 database, we have identified potential interactive partners suggesting their role in aminoglycosides resistance.</p><p><strong>Conclusion: </strong>Overexpressed proteins not only act to counteract or regulate drug effects but also have a role in protein dynamics that allow for resistance. Some of these identified proteins may serve as innovative drug targets and biomarkers for the early detection of drug-specific resistance in M.tb. Further research is needed to elucidate the mechanisms by which these potential protein targets contribute to resistance in AK and KM M.tb isolates.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"392-405"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603583","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}