Current protein & peptide science最新文献

{"title":"Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.","authors":"Rajesh Dabur","doi":"10.2174/0113892037393362251027073929","DOIUrl":"10.2174/0113892037393362251027073929","url":null,"abstract":"<p><p>Sciatic nerve injury represents a prevalent and incapacitating condition characterized by denervation, muscular atrophy, and compromised functionality. The Protein Kinase B (PKB)/ Akt signaling cascade serves as a vital modulator of skeletal muscle hypertrophy, metabolic processes, and regenerative capabilities. Subsequent to sciatic nerve injury, the PI3K/Akt signaling pathway exhibits dysregulation, exacerbating muscle atrophy and hindering recovery processes due to feedback inhibition of PKB/Akt phosphorylation by mTORC1, which consequently increases the expression of E3 ubiquitin ligases and causes muscle atrophy. Additionally, a multitude of other variables, encompassing neurotrophic factors, intracellular calcium ion concentrations, carboxyl-terminal modulator proteins, connexins, and tumor necrosis factor-α, either exert regulatory influences on Akt or are subject to regulation by Akt in a multifaceted manner. Hence, this review discusses the complex role of the PI3K/Akt signaling pathway in skeletal muscle dynamics following sciatic nerve injury, emphasizing its regulatory mechanisms and downstream effectors, and highlights strategies to target this pathway to enhance muscle regeneration and restore functional capabilities.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"362-373"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046010","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 Advances in Protein Kinase: From Concept to Clinic.","authors":"Shristi Singh, Ajita Paliwal, Niranjan Kaushik, Mridul Singh Sengar, Sweta Negi","doi":"10.2174/0113892037406748250901214051","DOIUrl":"10.2174/0113892037406748250901214051","url":null,"abstract":"<p><p>Protein kinase inhibitors (PKIs) are medicinal substances that target enzymes essential to vital cellular functions by controlling kinase activity. PKIs are being considered as targeted therapeutics to disrupt carcinogenic pathways since dysregulated kinase signalling is a hallmark of cancer. According to their binding mechanisms, PKIs are structurally categorised as follows: Type I inhibitors bind ATP competitively, Type II inhibitors target inactive kinase conformations, Type III inhibitors act through allosteric modulation, Type IV inhibitors operate independently of ATP, and Type V inhibitors, also referred to as covalent inhibitors, create irreversible bonds with target residues. PKIs have shown promise as a treatment for a number of malignancies, including leukemia, melanoma, lung, breast, and kidney cancers. While HER2-targeted PKIs have greatly improved results in breast cancer, targeting EGFR and ALK mutations has enhanced the treatment of lung cancer. Treatments for melanoma target BRAF and MEK inhibitors, while those for renal cell carcinoma concentrate on VEGF and mTOR pathways. Tyrosine kinase inhibitors have made significant strides in treating chronic myeloid leukemia, improving remission rates. Notwithstanding these achievements, resistance mechanisms still pose a threat to the efficacy of treatment, highlighting the necessity of continued investigation into next-generation PKIs and combination approaches to improve clinical outcomes for a range of cancer types. This article provides a comprehensive review of recent advancements in PKI research, including their mechanisms, therapeutic applications, and strategies to overcome drug resistance.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"533-545"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148002","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":"RGD Peptide-Based Hydrogel Enhances the Osteogenic Differentiation of Periodontal Ligament Stem Cells <i>via</i> Wnt Signaling.","authors":"Nadia Naeem, Muhammad Atif Siddiqui, Nazia Ahmed, Asma Saher Ansari, Kanwal Haneef","doi":"10.2174/0113892037389217250916074726","DOIUrl":"10.2174/0113892037389217250916074726","url":null,"abstract":"<p><strong>Introduction: </strong>Periodontitis results in progressive loss of gingival tissue and periodontal ligament, eventually resulting in tooth instability. As regenerating degraded periodontal tissue is not possible without intervention, therefore, a tissue-engineered substitute is a good option. Bone regeneration strategies often rely on either biochemical stimulation or engineered scaffolds, but rarely in a coordinated manner. Arginine-Glycine-Aspartic acid (RGD) hydrogel provides a unique combination of biocompatibility and biodegradability, making it an attractive scaffold for tissue engineering. The study aims to investigate the effect of combining Wnt pathway activation with Arginine-Glycine-Aspartic acid (RGD) hydrogel (a three-dimensional environment, 3D) to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs) derived from periodontal ligament tissue.</p><p><strong>Methods: </strong>The cells were isolated from the root of the extracted tooth. They were grown in an osteogenic medium with and without a Wnt activator in two-dimensional (2D) and RGD hydrogel- based 3D environments to expand in vitro. Osteogenic gene expression was evaluated by qPCR in 2D and 3D cultures. Mesenchymal stem cells isolated from periodontal ligament tissue showed osteogenic differentiation when cultured in a differential medium with or without the Wnt signaling activator, CHIR99021 (a GSK3β inhibitor).</p><p><strong>Results: </strong>The data of our study revealed that osteogenic genes were expressed in both 2D- and 3D-- cultured cells. However, higher expression of osteogenic genes was found in Wnt signaling-activated cells. Furthermore, the RGD hydrogel provided better differentiation efficacy and a significant increase (p < 0.001) in terms of Wnt-activated differentiation.</p><p><strong>Discussion: </strong>The RGD hydrogel-Wnt activation model described in this study holds strong potential for translation into preclinical bone regeneration strategies. By enhancing osteogenic differentiation through a synergistic interaction between the Wnt signaling pathway and the 3D peptide hydrogel matrix, this platform offers a promising approach to early-stage testing of bone regeneration therapies.</p><p><strong>Conclusion: </strong>Hence, the Arg-Gly-Asp (RGD) hydrogel-based 3D microenvironment along with a Wnt signaling activator provides superior efficacy in differentiation since it allows cell encapsulation and an environment that closely simulates native tissues. Therefore, these findings highlight the synergistic effect of biochemical and biophysical cues in directing stem cell fate and offer a promising strategy for advancing stem cell-based bone tissue engineering.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"598-611"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291433","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 Cdc42: Novel Approaches in Cardiovascular Disorders.","authors":"Rupali Chauhan, Sushma Devi, Thakur Gurjeet Singh","doi":"10.2174/0113892037392325250706122413","DOIUrl":"10.2174/0113892037392325250706122413","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, and need novel molecular targets for improved diagnosis and treatment. There are some potential new molecular targets for CVD treatment, including miRNAs, C-reactive protein, interleukins, fibrinogen, monocyte chemotactic protein-1, etc. One of the newer targets can be cell division control protein 42 homolog (Cdc42), a small GTPase of the Rho family, which has a significant role in cardiovascular physiology and pathology. This review focuses on demonstrating multifaceted functions of Cdc42 in cardiovascular complications, including vascular endothelial function, vascular smooth muscle cell regulation, cardiac myocyte development, inflammatory responses, and lipid metabolism. This review highlights the importance of Cdc42 in maintaining endothelial barrier integrity, regulating vascular smooth muscle cell phenotype, cardiac development, immune response modulation, and influencing lipid transport and insulin signalling. Furthermore, this review comprehensively explores the potential of Cdc42 as a biomarker for early CVD detection and proves to be a beneficial therapeutic target. This review also addresses the challenges in targeting Cdc42, given its ubiquitous nature, and directs future research, including tissue-specific modulation strategies and exploration of downstream signalling effectors. This review aims to potentiate future research by utilizing the current data on Cdc42 signalling in the cardiovascular system and constructing a bridge for innovative therapeutic approaches in CVD prevention and treatment. Cdc42 regulates cardiovascular processes, including endothelial function, vascular smooth muscle behaviour, cardiac development, inflammation, and metabolism. Additionally, evidence demonstrates Cdc42's involvement in key signalling pathways affecting lipid metabolism and insulin sensitivity.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"498-511"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752644","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":"A Study on the Rationality of Baicalein in the Treatment of Osteoporosis: A Narrative Review.","authors":"Qi Li, Xingyan Ma, Xiaodong Xu, Chengming Zhang, Weiguo Wang","doi":"10.2174/0113892037325783240912072039","DOIUrl":"10.2174/0113892037325783240912072039","url":null,"abstract":"<p><p>Baicalein (BN) is an active ingredient naturally present in Chinese herbs, such as Scutellaria baicalein, Coptis chinensis, and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered a potential natural medicine. Osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through MAPK/ERK and MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of action of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"416-424"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544256","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":"Profilin and Its Isoforms: Unravelling the Functional Diversity Across Life Forms.","authors":"Nupur Pathak, V Kohila","doi":"10.2174/0113892037390621250901052506","DOIUrl":"10.2174/0113892037390621250901052506","url":null,"abstract":"<p><p>The dynamic nature of the cell wall or plasma membrane is extremely important for the various cellular functions. The rearrangement of the cytoskeleton within the cell is a crucial process that is coordinated by the Profilin (PFN) protein. PFN is a small, cytosolic protein whose molecular weight is around 14-17 kDa. Originally, PFN was identified as an actin-binding protein that regulates actin dynamics. However, several studies later reported that the interaction of PFN with certain cytosolic proteins has a role in membrane trafficking, development, motility, and signaling. Additionally, the alternatively spliced PFN isoforms are present in different tissues and govern neurological and developmental functions. A mutation in these isoforms can result in abnormalities in the functioning. These isoforms interact with different ligands with certain specificity. However, the structural and functional biology of these isoforms is still under investigation. This review comprehensively discusses the roles of PFN and its isoforms across diverse species, spanning prokaryotes, eukaryotes, and viruses. Future research efforts are crucial for elucidating novel aspects and enhancing our understanding of the molecular mechanisms governed by PFN and its isoforms.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"564-580"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136667","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":"Aquatic BPI/LBPs: A Promising Antimicrobial Peptide Resource for Disease Control in Aquaculture.","authors":"Jingxian Sun, Huiqi Deng, Bingyu Ning, Yaoyao Zhan, Yaqing Chang","doi":"10.2174/0113892037364423250516032256","DOIUrl":"10.2174/0113892037364423250516032256","url":null,"abstract":"<p><p>Aquaculture is currently the fastest-growing food supply industry worldwide. Disease control has always been a core concern in the sector of aquaculture. In recent years, the frequency of aquaculture disease outbreaks has increased dramatically due to the continuously increased antibiotic resistance of pathogens. Therefore, it is imperative to find effective antibiotic alternatives for disease control in aquaculture. Bactericidal permeability increasing/lipopolysaccharide binding proteins (BPI/LBPs) are endogenous peptides ubiquitously expressed in aquatic animals that exhibit antimicrobial effects similar to antibiotics. This review presents an overview of current research on BPI/LBPs derived from aquatic animals, the predicted antimicrobial mechanisms of aquatic BPI/LBPs, and the application potential and prospects of aquatic BPI/LBPs as an antimicrobial peptide (AMP) resource. To sum up, the systematic research on aquatic BPI/LBPs may not only enrich AMP resources but also provide new clues for the development of eco-friendly disease control strategies in aquaculture.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"1-17"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186755","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":"A Review on the Pathophysiology of Alzheimer's Disease.","authors":"Uma Agarwal, Garima Kapoor, Rajiv Kumar Tonk","doi":"10.2174/0113892037416859250915091846","DOIUrl":"10.2174/0113892037416859250915091846","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Alzheimer's disease is characterized by a complex and multifactorial pathogenesis, involving key features such as amyloid-beta plaques, tau tangles, and neuron loss. Understanding the disease requires investigating its underlying causes, as these hallmarks reflect the intricate physiological processes involved. Identifying the root factors driving AD is essential for developing effective treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This literature review was conducted using PubMed and Scopus databases, covering studies published from October 1999 to April 2025. The review included 190 references focused on the pathophysiology of Alzheimer's disease (AD). The selected studies analysed the primary pathophysiology leading to AD, particularly the accumulation of amyloid-beta plaques, tau tangles, and neuronal loss.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study highlights several key biological factors associated with Alzheimer's Disease (AD). These include genetic mutations, mitochondrial dysfunction, hormonal imbalances, inflammation, oxidative stress, cellular division abnormalities, and reduced levels of dopamine-related neurotransmitters. It also highlights issues with calcium regulation and the imbalance of metals, such as copper, iron, lead, and zinc, in the body. Lifestyle choices such as drinking alcohol and smoking, along with changes in blood vessels and problems with the blood-brain barrier, were also found to play a role in how the disease develops. Additionally, the presence of certain pathogens was suggested as a possible factor in the disease's underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The results indicate that a complex combination of genetic, biochemical, and environmental factors shapes the development and progression of Alzheimer's disease. Genetic mutations seem to play a significant role in affecting enzyme functions, which can disrupt vital biological processes. Problems with mitochondria and hormonal imbalances contribute to the deterioration of nerve cells, while oxidative stress and neuroinflammation are key mechanisms that worsen cellular damage. Disruptions in calcium signalling and imbalances in bio-metals further disturb neuronal stability. Lifestyle choices, blood vessel issues, and blood-brain barrier problems highlight the multifaceted nature of the disease. The study also highlights the close relationship between oxidative stress and neuroinflammation, suggesting that they may form a feedback loop that accelerates disease progression. Additionally, the possible involvement of infectious agents adds another layer of complexity, indicating that infections might trigger or worsen neurodegeneration in vulnerable individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;To better understand and address Alzheimer's disease, it is essential to examine the fundamental processes that trigger its development. The various and interconnected factors involved- such as genetic mutations, cellular ","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"581-597"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307084","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":"Siglecs: From Biomodulation to Immunotherapy.","authors":"Jia Chen, Yumin Huang, Yafei Wang, Tianlei Sun, Congcong Li, Yuan Feng, Zhenbiao Wu","doi":"10.2174/0113892037372672250605183318","DOIUrl":"10.2174/0113892037372672250605183318","url":null,"abstract":"<p><strong>Background: </strong>Sialic acid-binding immunoglobulin-like lectins (Siglecs) are cell-surface immunological receptors predominantly expressed on immune cells such as monocytes, macrophages, and dendritic cells. They play a crucial role in regulating inflammatory processes in various diseases and serve as immunological checkpoints in cancer. Despite several immune checkpoint inhibitors targeting Siglecs having entered clinical trials, the number of Siglec-targeted immunotherapies remains limited.</p><p><strong>Objective: </strong>This review aims to investigate the contributions of Siglecs in human diseases and explore novel therapeutic strategies targeting the Siglec-sialic acid immunological axis.</p><p><strong>Methods: </strong>The authors systematically searched PubMed, Web of Science, and Google Scholar for publications mainly from 2015-2025, using search terms related to Siglecs, tumors, autoimmune diseases, and specific Siglec subtypes (CD169, Siglec2). Studies were included if they examined Siglecs biology, immunomodulation, or immunotherapeutic potential. Studies not directly relevant to Siglecs function/therapeutics and non-peer-reviewed materials (conference abstracts, editorials) were excluded. Screening was done via titles and abstracts with data referenced from research article results, and eligible articles underwent full-text review for final inclusion.</p><p><strong>Results: </strong>The analysis reveals that Siglecs exhibit dual functions, acting as both activators and inhibitors of immune responses. They are implicated in the pathogenesis of various diseases, including cancer, autoimmune disorders, and viral infections. Several Siglec-targeted immunotherapies are currently in clinical trials, demonstrating their potential in disease management. For instance, Siglec15 and Siglec10 have been identified as potential immune checkpoints in cancer, while Siglec2 and Siglec10 play roles in autoimmune diseases like systemic lupus erythematosus (SLE).</p><p><strong>Conclusion: </strong>Siglecs are key immunomodulators that mediate cell-cell and pathogen interactions, playing pivotal roles in human diseases. Further research into their mechanisms and clinical applications is essential to fully harness their therapeutic potential. Targeting Siglecs offers promising avenues for developing novel immunotherapies, particularly in cancer and autoimmune diseases.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"163-181"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552550","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":"From CASP13 to the Nobel Prize: DeepMind's AlphaFold Journey in Revolutionizing Protein Structure Prediction and Beyond.","authors":"Jad Abbass","doi":"10.2174/0113892037374986250711152300","DOIUrl":"10.2174/0113892037374986250711152300","url":null,"abstract":"<p><p>Four years ago, at the 14th Critical Assessment of Structure Prediction (CASP14), John Moult made a historic announcement that the long-standing challenge of Protein Structure Prediction- a problem that had confounded scientists for over five decades-had been \"solved\" for single protein chains. Supporting this groundbreaking statement was a plot depicting the median Global Distance Test (GDT) across 87 out of 92 domains, where AlphaFold2, developed by DeepMind, achieved an unprecedented score of 92.4. The bar chart not only underscored AlphaFold2' s remarkable performance-standing out prominently among other methods-but also revealed a level of accuracy that exceeded all prior expectations. In the years since this breakthrough, DeepMind's team has made significant strides. The AlphaFold Database now hosts approximately 214 million structures for various model organisms, covering nearly the entire genome. Research continues to explore multiple facets of protein science, including the prediction of multi-chain protein complex structures and the impact of missense mutations on protein function. The open availability of this extensive database and the suite of AlphaFold2 algorithms has catalysed remarkable advancements in protein biology and bioinformatics. This review will begin by revisiting DeepMind's early efforts in CASP13, detailing the architecture and the remarkable progress that led to their breakthrough of AlphaFold2 in CASP14 (2020). It will then delve into two main areas: (1) AlphaFold's contributions to the scientific community across various fields over the past four years, and (2) the latest improvements, enhancements, and achievements by DeepMind, including AlphaFold3 and the Nobel Prize in Chemistry.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"111-130"},"PeriodicalIF":2.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231624","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}