Current protein & peptide science最新文献

{"title":"Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.","authors":"Shikha Rani, Minkal Tuteja","doi":"10.2174/0113892037338028241230092414","DOIUrl":"10.2174/0113892037338028241230092414","url":null,"abstract":"<p><p>The three-dimensional structure of proteins, achieved through the folding of the nascent polypeptide chain <i>in vivo</i>, is largely facilitated by molecular chaperones, which are crucial for determining protein functionality. In addition to aiding in the folding process, chaperones target misfolded proteins for degradation, acting as a quality control system within the cell. Defective protein folding has been implicated in a wide range of clinical conditions, including neurodegenerative and metabolic disorders. It is now well understood that the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease shares a common mechanism: the accumulation of misfolded proteins, which aggregate and become toxic to cells. Among the family of molecular chaperones, Heat Shock Proteins (HSPs) are highly expressed in response to cellular stress and play a pivotal role in preventing protein aggregation. Specific chaperones, particularly HSPs, are now recognized as critical in halting the accumulation and aggregation of misfolded proteins in these conditions. Consequently, these chaperones are increasingly considered promising pharmacological targets for the treatment of protein aggregation-related diseases. This review highlights research exploring the potential roles of specific molecular chaperones in disorders characterized by the accumulation of misfolded proteins.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"451-466"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051908","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":"TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.","authors":"Sakshi Kumar, Vikram Sharma, Shikha Yadav","doi":"10.2174/0113892037324425241018061548","DOIUrl":"10.2174/0113892037324425241018061548","url":null,"abstract":"<p><p>TLR4 stands at the forefront of innate immune responses, recognizing various pathogen- associated molecular patterns and endogenous ligands, thus serving as a pivotal mediator in the immune system's defense against infections and tissue damage. Beyond its canonical role in infection, emerging evidence highlights TLR4's involvement in numerous non-infectious human diseases, ranging from metabolic disorders to neurodegenerative conditions and cancer. Targeting TLR4 signaling pathways presents a promising therapeutic approach with broad applicability across these diverse pathological states. In metabolic disorders such as obesity and diabetes, dysregulated TLR4 activation contributes to chronic low-grade inflammation and insulin resistance, driving disease progression. In cardiovascular diseases, TLR4 signaling promotes vascular inflammation and atherogenesis, implicating its potential as a therapeutic target to mitigate cardiovascular risk. Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, exhibit aberrant TLR4 activation linked to neuroinflammation and neuronal damage, suggesting TLR4 modulation as a strategy to attenuate neurodegeneration. Additionally, in cancer, TLR4 signaling within the tumor microenvironment promotes tumor progression, metastasis, and immune evasion, underscoring its relevance as a target for anticancer therapy. Advances in understanding TLR4 signaling cascades and their contributions to disease pathogenesis have spurred the development of various pharmacological agents targeting TLR4. These agents range from small molecule inhibitors to monoclonal antibodies, with some undergoing preclinical and clinical evaluations. Furthermore, strategies involving TLR4 modulation through dietary interventions and microbiota manipulation offer additional avenues for therapeutic exploration. Hence, targeting TLR4 holds significant promise as a therapeutic strategy across a spectrum of human diseases, offering the potential to modulate inflammation, restore immune homeostasis, and impede disease progression.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"241-258"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892750","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 Study of Lactogenic Effect and Milk Nutritional Density of Oral Galactagogue in Female Rabbit.","authors":"Saurabh Maru, Sateesh Belemkar","doi":"10.2174/0113892037300581240830052536","DOIUrl":"10.2174/0113892037300581240830052536","url":null,"abstract":"<p><strong>Background: </strong>Hypogalactia and agalactia in lactating mothers are the major causes of child malnutrition, mortality, morbidity, and overall ill health. The development of such treatments requires a well-designed preclinical study with suitable laboratory animals, which needs to be improved. Thus, a suitably designed study with a laboratory animal to analyse galactagogue activity, along with an assessment of the quality and quantity of milk, is required.</p><p><strong>Objectives: </strong>This study aimed to evaluate the potential of rabbit as an animal model for studying lactogenic activity.</p><p><strong>Methods: </strong>The structural homology of prolactin, gene prolactin receptor, and prolactin hormone in humans, rabbit, and rat was studied using BLAST and PyMol to assess similarity in the lactogenic system. Daily and cumulative milk production and pre-treatment (control) and post-treatment (three drugs) in rabbits were recorded and evaluated by analysing protein, fat, lactose, solid non-- fat, and ash values. All parameters were recorded on the 0th day and at the end of weeks 1, 2, and 3. Mammary gland histopathology was performed to evaluate the effects on mammary glands.</p><p><strong>Results: </strong>Homology studies revealed that the sequences of the human and rabbit prolactin genes, receptors, and hormones had a high similarity index. Treatment with Domperidone, Metoclopramide, and Shatavari significantly enhanced milk production by enhancing prolactin secretion; only Shatavari increased milk nutrition. Enlargement of the tubuloalveolar ducts of the mammary glands was observed.</p><p><strong>Conclusion: </strong>Our findings suggest that rabbits are robust, reproducible, ethically superior, and preclinically relevant animals for assessing lactogenic activity.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"125-138"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125023","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":"Unveiling the Emerging Role of Klotho: A Comprehensive Narrative Review of an Anti-aging Factor in Human Fertility.","authors":"Naina Kumar","doi":"10.2174/0113892037329291240827113808","DOIUrl":"10.2174/0113892037329291240827113808","url":null,"abstract":"<p><p>Klotho, an anti-aging protein, plays a vital role in diverse biological functions, such as regulating calcium and vitamin D levels, preventing chronic fibrosis, acting as an antioxidant and anti-inflammatory agent, safeguarding against cardiovascular and neurodegenerative conditions, as well as exerting anti-apoptotic, anti-senescence effects. Additionally, it contributes to metabolic processes associated with diabetes and exhibits anti-cancer properties. This protein is commonly expressed in organs, such as kidneys, brain, pancreas, parathyroid glands, ovaries, and testes. Recent research has highlighted its significance in human fertility. This narrative review provides insight into the involvement of Klotho protein in male and female fertility, as well as its potential role in managing human infertility in the future. In this study, a search was conducted on literature spanning from November 1997 to June 2024 across multiple databases, including PUBMED, SCOPUS, and Google Scholar, focusing on Klotho proteins. The search utilized keywords, such as \"discovery of Klotho proteins,\" \"Biological functions of Klotho,\" \"Klotho in female fertility,\" \"Klotho and PCOS,\" \"Klotho and cryopreservation,\" and \"Klotho in male infertility.\" Inclusion criteria comprised full-length original or review articles, as well as abstracts, discussing the role of Klotho protein in human fertility, published in English in various peer-reviewed journals. Exclusion criteria involved articles published in languages other than English. Hence, due to its anti-aging characteristics, Klotho protein presents potential roles in male and female fertility and holds promising prospects for reproductive medicine. Further, it holds the potential to become a valuable asset in addressing infertility concerns for both males and females.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"105-112"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119203","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":"Current Trends and Challenges in Targeting Tumor Mitochondrial Glycolysis and Oxidative Phosphorylation Pathways for Cancer Therapy.","authors":"Rahul Pratap Singh, Sonali","doi":"10.2174/0113892037307636240612112408","DOIUrl":"10.2174/0113892037307636240612112408","url":null,"abstract":"","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"2-5"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497345","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":"Insights into the Binding of Metadoxine with Bovine Serum Albumin: A Multi-Spectroscopic Investigation Combined with Molecular Docking.","authors":"Harman Deep Kour, Apoorva Pathania, Anu Radha Pathania","doi":"10.2174/0113892037318575240919054053","DOIUrl":"10.2174/0113892037318575240919054053","url":null,"abstract":"<p><strong>Background: </strong>Metadoxine, also known as pyruvate dehydrogenase activator, is a small molecule drug that has been used in the treatment of various medical conditions. Bovine serum albumin is a commonly studied protein that serves as a plasmatic for understanding protein-drug interactions due to its abundance.</p><p><strong>Objective: </strong>This research suggests that metadoxine can bind to bovine serum albumin with moderate affinity, leading to an alteration in the secondary structure of the protein, which may also influence the protein's stability and function, which could provide a comprehensive understanding of the interaction at a molecular level. In this study, a variety of methodologies wereused to determine various thermodynamic parameters.</p><p><strong>Methods: </strong>The study uses UV-visible, Fluorescence, Fourier-transform infrared, Circular dichroism spectroscopy, and Molecular docking to analyze the interaction between bovine serum albumin and metadoxine, providing thermodynamic parameters for understanding the protein structure and its binding.</p><p><strong>Result: </strong>The binding of metadoxine with bovine serum albumin, causes a hyperchromic shift. In fluorescence spectroscopy, the value of the Stern Volmer increases constantly with an increase in temperature, suggesting a stronger interaction between the Metadoxine and the Bovine serum albumin, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism indicated a reduction in the secondary structure of Bovine serum albumin.</p><p><strong>Conclusion: </strong>The interactions between metadoxine and bovine serum albumin, cause hyperchromic shift revealed by UV-visible spectroscopy, whereas in Fluorescence spectroscopy, the value of the Stern Volmer constant increases with an increase in temperature, suggesting a stronger interaction between the MD and the BSA, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism spectroscopy indicated a reduction in the secondary structure of the protein, as evidenced by the shifting of the amide II band and leading to a slight decrease in the α- helix content. The molecular docking shows that metadoxine was docked in the subdomain IIA binding pocket of BSA.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"213-225"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544257","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":"PPA1, TRIM68 and FBXO46: Potential Therapeutic Targets for Triple Negative Breast Cancer.","authors":"Fatima Haider, Nida Syed, Syeda Abiha Zehra Jaffari, Basir Syed, Aftab Ahmed, Shamshad Zarina, Zehra Hashim","doi":"10.2174/0113892037334325241014053319","DOIUrl":"10.2174/0113892037334325241014053319","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.</p><p><strong>Methods: </strong>The cell cytotoxicity of ML364 (2-(4-Methylphenylsulfonamido)-N-(4-phenylthiazol- 2-yl)-4-(trifluoromethyl)benzamide) was measured at different concentrations in TNBC-treated and untreated cells. The 2DE and LC-MS/MS analysis were used for protein identification of differentially expressed proteins. Furthermore, the quantitation of gene expression was demonstrated using RT-qPCR. TIMER, HPA, and UALCAN databases were utilized for further analysis.</p><p><strong>Results: </strong>Differentially expressed proteins and genes after ML364 treatment in TNBC were found to be linked with the USP2 (ubiquitin specific peptidase 2)-mediated pathway. Our results demonstrate that differentially identified proteins, including PPA1, TRIM68, and FBXO46, could be a potential prognostic biomarker for TNBC. Further analysis through the UALCAN and HPA databases shows the high expression of these proteins in primary breast tumors, which is in contrast to normal. The induction of ML364 significantly reduced the expression of PPA1, TRIM68, and FBXO46 proteins and induced cell cytotoxicity in TNBC cells.</p><p><strong>Conclusion: </strong>This study provides an understanding of the USP2-mediated signaling pathway in TNBC, emphasizing the role of USP2 and its substrates with apoptotic genes. Our results offer insight into the USP2-mediated cellular mechanism after ML364 treatment in TNBC that could be a potential therapeutic candidate.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"365-377"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926724","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 Lactate in Ischemic Stroke: As an Energy Source and Signaling Molecule.","authors":"Rui Zhang, Xintong Li, Kemeng Liu, Meng Yang, Peiliang Dong, Hua Han","doi":"10.2174/0113892037335945241029111720","DOIUrl":"10.2174/0113892037335945241029111720","url":null,"abstract":"<p><p>Stroke is an acute cerebrovascular disease that causes brain tissue damage due to sudden blockage or rupture of blood vessels in the brain. According to the latest data from the Global Burden of Disease Study, the number of stroke patients worldwide is estimated to exceed 100 million, and more than 80% of patients suffer from stroke. Ischemic stroke is a type of stroke due to which two-thirds of the patients are disabled or even die, seriously affecting the patient's quality of life. Lactate is an indispensable substance in various physiological and pathological cells and plays a regulatory role in different aspects of energy metabolism and signal transduction. Studies have found that during cerebral ischemia and hypoxia, lactate concentration increases significantly, improving the energy supply to the ischemic area. Based on the scientific concept of lactate travelling through the brain, this article focuses on the important role of lactate as an energy source after ischemic stroke and analyzes the relationship between lactate as a signaling molecule and neuroprotection, angiogenesis, and anti-inflammatory effects. The aim of this study is to outline the molecular mechanisms by which lactate exerts its different effects in ischemic stroke. Some references are provided in this study for the research on lactate therapy for ischemic stroke.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"334-351"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929973","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":"Amyloid-β Clearance with Monoclonal Antibodies: Transforming Alzheimer's Treatment.","authors":"Rabab Fatima, Yumna Khan, Mudasir Maqbool, Prasanna Srinivasan Ramalingam, Mohammad Gayoor Khan, Ajay Singh Bisht, Md Sadique Hussain","doi":"10.2174/0113892037362037250205143911","DOIUrl":"10.2174/0113892037362037250205143911","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive condition that causes the degeneration of nerve cells, leading to a decline in cognitive abilities and memory impairment, significantly affecting millions around the globe. The primary pathological feature of AD is the buildup of amyloid-β (Aβ) plaques in the brain, which has become a major target for therapeutic strategies. This thorough review examines the progress made in next-generation therapies that concentrate on monoclonal antibodies (mAbs) aimed at Aβ. We explore how these antibodies function, their effectiveness in clinical settings, and their safety profiles, specifically discussing notable mAbs, such as aducanumab, donanemab, lecanemab, etc. This review also addresses the difficulties related to Aβ- targeted treatments. Furthermore, it examines the advancing field of biomarker development and tailored medicine strategies designed to improve the accuracy of AD treatment. By integrating the latest findings from clinical trials and new research, this review offers an in-depth evaluation of the possibilities and challenges associated with mAbs in modifying the progression of AD. Future considerations regarding combination therapies and novel drug delivery methods are also examined, emphasizing the necessity for ongoing research to achieve significant advancements in managing AD. Through this review, we seek to provide clinicians, researchers, and policymakers with insights into the current landscape and future directions of Aβ-targeted therapies, promoting a deeper understanding of their role in addressing AD.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"515-545"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467250","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":"Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/β-Catenin Pathway.","authors":"Ziyan Jiang, Shiyun Huang, Tingting Ying, Lenan Liu, Yufei Han, Runrun Feng, Haiyan Sun, Ceng Cao, Qing Zuo, Zhiping Ge","doi":"10.2174/0113892037332988240816052550","DOIUrl":"10.2174/0113892037332988240816052550","url":null,"abstract":"<p><strong>Introduction: </strong>Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear.</p><p><strong>Materials and methods: </strong>The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/β-catenin pathway.</p><p><strong>Results: </strong>In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and β-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/β-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells.</p><p><strong>Conclusion: </strong>Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/β-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"156-166"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016658","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}