Advances in protein chemistry and structural biology最新文献

{"title":"Marine-Derived bioactives as precision modulators of molecular targets: Emerging paradigms in therapeutic design.","authors":"Solaiyappan Ramanathan, Kothaimanimaran Brindha, Periyasamy Vijayalakshmi, Kumar Viknesh, Antony Likson, Deepali Desai, Chandrabose Selvaraj","doi":"10.1016/bs.apcsb.2026.04.001","DOIUrl":"10.1016/bs.apcsb.2026.04.001","url":null,"abstract":"<p><p>Oceanic environments represent a unique source of biologically active substances, which has a large spectrum of chemical composition, and has significant therapeutic potential. Marine-derived bioactive compounds have emerged as accuracy regulators of molecular signals and offer new options to modern therapeutics design. Unlike normal small molecules, these compounds are often highly specific in terms of interaction with challenging targets, including proteases, chaperones, protein-protein interaction crossroads, transcription factors, and epigenetic regulators. It is becoming clear that they have the ability to shape disease specific gene expression and cellular phenotypes through chromatin architecture, altering complex signaling networks, and immunological checkpoints. Such system level regulation is particularly relevant in multifactorial diseases including neurological diseases, cancer, and chronic inflammatory states. The advances in structural biology, computational drug design and the omics technologies have minimized reliance on direct marine harvesting and accelerated the discovery and optimization of marine biological agents. Moreover, the concept of marine-inspired scaffolds is integrated into the framework of precision medicine more often, making it possible to develop a personalized therapeutical strategy that is less risky and more efficient. This review highlights recent mechanistic findings, targets, and translational advancements of marine-derived bioactives with a focus on the importance of these advancements in the development of next-generation therapeutics based on their revolutionary nature.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"153 ","pages":"409-436"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological microtubule dynamics in Parkinson's disease: Mechanisms and therapeutic implications.","authors":"Kirti Baghel, Ateendra Kumar Dubey, Satyendra Singh, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2025.10.019","DOIUrl":"10.1016/bs.apcsb.2025.10.019","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily marked by the degeneration of dopaminergic neurons in the substantia nigra and the pathological accumulation of misfolded α-synuclein in Lewy bodies. This chapter explores the underrecognized role of microtubule (MT) dysregulation in PD pathogenesis, linking disruptions in cytoskeletal integrity to impaired axonal transport and neuronal survival. The fundamental biology of MTs, their dynamics, and their regulation by motor proteins and associated proteins like MT-associated proteins (MAPs), tau, and gamma-tubulin complexes. Special attention is given to how mutations linked to PD, such as those in SNCA (α-synuclein), Parkin, PINK1 (PTEN-induced kinase 1), and LRRK2 (leucine-rich repeat kinase 2), lead to MT destabilization, impaired mitophagy, and disruptions in axonal transport. A self-perpetuating cycle of MT disruption and α-synuclein aggregation is proposed, resulting in synaptic failure and dopaminergic neuron loss. The chapter also evaluates emerging therapeutic strategies targeting MT stabilization, including LRRK2 inhibitors, MT-stabilizing agents like Epothilone D, and approaches to modulate α-synuclein aggregation. Challenges such as the blood-brain barrier, off-target effects of MT-targeting drugs, and patient-specific variability in drug response are critically discussed. The future directions include CRISPR-Cas9-based gene therapies and personalized medicine, emphasizing the need for a deeper understanding of PD-related molecular pathways. This comprehensive overview highlights MT dynamics not just as collateral damage but as a central element in PD pathology, offering novel insights into potential avenues for intervention.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"423-443"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular chaperones mediated proteostasis depletion: A cause of neurodegeneration?","authors":"Sumit Kinger, Akash Choudhary, Prashant Kumar, Yuvraj Anandrao Jagtap, Vivek Sharma, Rohan Dhiman, Amit Prasad, Rahul Verma, Subashchandrabose Chinnathambi, Amit Mishra","doi":"10.1016/bs.apcsb.2025.10.033","DOIUrl":"10.1016/bs.apcsb.2025.10.033","url":null,"abstract":"<p><p>Protein homeostasis is a critical aspect of cellular homeostasis as proteins are one of the most diverse biomolecules, responsible for multiple molecular and cellular functions. Protein quality control machinery is essential for maintaining integrity of cellular proteome via regulating its synthesis, structure, function, and degradation. Molecular chaperones are central to the protein quality control apparatus of cells and assist in folding nascent polypeptides, maturation, sequestration, solubilisation, and degradation of proteins. The coordination and cooperation between multiple cellular chaperones and other quality control elements, such as ubiquitin-proteasome system and autophagy, form a network, critical for proteostasis. Disturbed proteostasis and protein aggregation are hallmark features of neurodegenerative diseases. Re-establishing cellular proteostasis and enhancing chaperones' levels and functions can alleviate protein aggregation and associated cytotoxicity. Here, we have explored the potential of abundant cellular chaperone Hsp90, large chaperone Hsp110, small chaperone Hsp27, and anti-oxidant and mitoprotective chaperone DJ-1 in the regulation of proteostasis, with implications for neurodegenerative diseases, Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. We have focused on roles and mechanisms of function of these chaperones in countering disturbed proteostasis in neurodegenerative disorders.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"181-219"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioanalytical approaches applied to identify cytoskeletal proteins associated with neurodegenerative diseases.","authors":"Cícero Alves Lopes Júnior, Carla Mariana da Silva Medeiros, Mikael Kélvin de Albuquerque Mendes, Clecio Dantas, Tatianny A Andrade, Jemmyson Romário de Jesus","doi":"10.1016/bs.apcsb.2025.10.022","DOIUrl":"10.1016/bs.apcsb.2025.10.022","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) are a heterogeneous group of progressive disorders characterized by the selective loss of neuronal structure or function, often leading to cognitive and/or motor dysfunction. Although NDs present clinical diversity, several of these diseases share a common pathological characteristic, which consists of the aggregation of cytoskeletal proteins in specific regions of the central nervous system (CNS). The cytoskeleton is an intricate network of filamentous proteins within the cytoplasm and plays a critical role in maintaining neuronal polarity, axonal transport, synaptic integrity, and overall cellular architecture. Structural and functional abnormalities in the cytoskeleton, especially in neuronal intermediate filament (IF) proteins and microtubule-associated protein tau (MAPT), can compromise neuronal function, inciting inflammation and leading to neuron cell death. So, cytoskeletal protein species can be considered biomarkers and provide guidance for treatments associated with NDs. Considering the complexity of the biological matrix and the molecular mechanisms involved, the identification and characterization of cytoskeletal protein abnormalities require robust and sensitive analytical tools, comprising sample preparation protocol, advanced instrumental techniques and data processing algorithms. So, this chapter provides a comprehensive review of the bioanalytical approaches employed in the investigation of cytoskeletal proteins involved in the pathogenesis of NDs. Also, some tools applied in data processing are discussed here, considering the combination of classical data analysis algorithms with artificial intelligence focused on the discovery of cytoskeletal biomarker proteins. Furthermore, a general discussion of the possible molecular mechanisms related to neuronal degeneration involving the main cytoskeletal proteins is presented.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"445-487"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-protein coupled receptor chemokine CX3CR1 influences extracellular Tau internalization in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Nagaraj Rangappa, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2025.10.023","DOIUrl":"10.1016/bs.apcsb.2025.10.023","url":null,"abstract":"<p><p>Alzheimer's Disease is characterized by significant alterations in the cytoskeleton, driven by hyperphosphorylation of the microtubule-associated protein Tau. This modification impairs Tau's ability to stabilize microtubules, leading to structural instability, disrupted axonal transport, and neuronal degeneration. Hyperphosphorylated Tau aggregates into neurofibrillary tangles and oligomers, exacerbating cellular dysfunction. The cytoskeleton, composed of actin filaments, microtubules, and intermediate filaments, is vital for maintaining cellular structure, intracellular transport, and signalling. G-protein coupled receptors, widely expressed in neuroglial cells, play critical roles in neuroinflammation, synaptic pruning, and cytoskeletal dynamics in neurodegenerative diseases. Extracellular Tau species interact with GPCRs, particularly in microglia and astrocytes, triggering neuroinflammatory responses and cytoskeletal remodelling. Key kinases such as Glycogen Synthase Kinase-3β and Cyclin-Dependent Kinase-5 regulate Tau phosphorylation. Hyperactivation of these kinases, influenced by GPCRs signalling pathways, promotes Tau hyperphosphorylation, contributing to Tauopathies. Stress-related GPCRs like CRFR1, β2AR, and AT2R, along with glutamate-driven activation of mGluR2, exacerbate Tau pathology by enhancing kinase activity. Conversely, certain GPCRs, such as mAChRs, can mitigate Tau hyperphosphorylation by inhibiting GSK-3β activity. Understanding the interplay between Tau, GPCRs, and associated signalling pathways provides insights into the molecular mechanisms driving AD and highlights potential therapeutic targets for mitigating Tauopathies and neurodegeneration.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"319-349"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chemistry and molecular basis of cultured meat from alternative proteins.","authors":"Irene P Daet, Ashokkumar Sibiya","doi":"10.1016/bs.apcsb.2026.08.006","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.08.006","url":null,"abstract":"<p><p>As global protein demand increases, cultured meat from alternative protein systems represents an innovative approach to addressing sustainability and food safety concerns. This chapter provides an overview of the chemistry and molecular basis underlying in vitro meat production, focusing on cellular sources, stem cell biology, cellular differentiation, and scaffold materials. The controlled proliferation and differentiation of muscle and adipose cells are governed by biochemical pathways that regulate lipid biosynthesis, oxidative balance, and structural organization. Bioreactor systems and metabolic pathway engineering collectively influence structural integrity, nutritional composition, and sensory properties. Moreover, redox biology, oxidative stability, food safety considerations, and life-cycle sustainability are discussed as critical determinants of product quality and environmental performance. By integrating molecular mechanisms with food chemistry and process engineering, this chapter contributes to advancing scalable, safe, and nutritionally optimized cultured meat systems for future food security.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"154 ","pages":"593-625"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational structural insights into alternative proteins: The impact of AlphaFold and AI-based prediction.","authors":"Shiammala Periyasamy Natarajan, Bagavathi Lakshmi Ramarajan, Rani Sivakumar, Jayaprakashvel Mani","doi":"10.1016/bs.apcsb.2026.08.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.08.004","url":null,"abstract":"<p><p>Proteins are fundamental biomolecules composed of amino acids linked by peptide bonds, forming complex macromolecules that determine cellular structure and biological function. The three-dimensional conformation of proteins plays a crucial role in defining their biochemical activity, stability, and interactions. In the emerging field of alternative proteins, such as microbial, algal, plant-based, and precision-fermented proteins, understanding structural organization is essential for improving functional properties including digestibility, nutritional value, texture, and enzymatic performance. Experimental determination of protein structures through conventional techniques remains time-consuming, technically demanding, and expensive. Recent advancements in artificial intelligence have revolutionized protein structure prediction, particularly with the development of AlphaFold by Google DeepMind. AlphaFold integrates deep learning algorithms, attention mechanisms, and evolutionary information derived from multiple sequence alignments to accurately predict spatial relationships among amino acid residues. Its performance has been validated through the Critical Assessment of Structure Prediction (CASP) competitions, demonstrating unprecedented accuracy in computational structure prediction. The application of AlphaFold provides significant opportunities for accelerating research in alternative proteins by enabling rapid structural characterization, enzyme engineering, and functional optimization of novel protein sources. This review highlights the scientific developments that led to AlphaFold, describes its architectural innovations, and discusses its potential applications in alternative protein discovery, design, and processing. Furthermore, current limitations and future perspectives in AI-assisted structural prediction for sustainable protein production are discussed.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"154 ","pages":"469-497"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial peptides and proteins: Mechanism of action and therapeutic potential.","authors":"Ateendra Kumar Dubey, Amit Mishra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2025.07.001","DOIUrl":"10.1016/bs.apcsb.2025.07.001","url":null,"abstract":"<p><p>With the ever-increasing challenge of antibiotic resistance and the rise in multidrug-resistant strain-associated mortality, antimicrobial peptides and proteins have emerged as a potential therapeutic solution. Antimicrobial peptides (AMPs) are host defence peptides that not only display activity against several pathogens but have been utilised clinically to treat infections caused by multidrug and pan-drug resistant superbugs, working in synergy with existing therapeutics for better clinical outcomes. The chapter discusses clinical perspectives of AMPs, beginning with the fundamentals to current clinical perspectives and challenges faced in AMP research, along with their solutions. The chapter gives detailed insight into the pharmacology of all clinically approved AMPs, including their pharmacokinetics and mechanism of action. Further, the chapter explores various peptide modifications and peptide delivery methods to increase therapeutic potency and applicability of these peptides, and artificial intelligence-based computational tools and databases that can be utilised for peptide prediction and accelerate AMP discovery.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"143-170"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteriophage endolysins: A promising therapeutic strategy against drug- resistant Staphylococcus aureus.","authors":"Niranjana Rajesh, Jaya Bisht, Thulasi Sunilkumar, Alana Sibi, Dileep Francis","doi":"10.1016/bs.apcsb.2025.09.001","DOIUrl":"10.1016/bs.apcsb.2025.09.001","url":null,"abstract":"<p><p>Staphylococcus aureus infections are difficult to treat due to the widespread emergence of antibiotic resistant strains, complex virulence mechanisms, and the ability to form recalcitrant biofilms. Infections with multi-drug resistant variants such as the methicillin resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) lead to increased morbidity and mortality and result in higher treatment cost compared to those with sensitive strains. While vaccines are sought as a preventive strategy, a clinically viable vaccine has not surfaced yet. Considering the rapid dissemination of resistant strains across the globe, the World Health Organisation has categorised S. aureus as an ESKAPE pathogen that requires the immediate development of alternative therapeutics. One of the most promising alternative to conventional antibiotics are bacteriophage endolysins, a family of peptidoglycan hydrolases capable of destabilising the peptidoglycan cell wall in bacteria by cleaving essential bonds in the peptidoglycan structure. Bacteriophages employ these for lysing the host cell during the last stage of their lytic life cycle to release progeny virions. A study published in 2001 demonstrated that purified endolysins can lyse bacterial cells rapidly and effectively when administered exogenously. Endolysins offer many advantages over conventional antibiotics: they are not likely to develop resistance as they target a highly conserved and indispensable component of the bacterial cell wall; they act faster than conventional antibiotics; they are species-selective in their lytic activity, sparing non-target organisms. Despite the numerous challenges in their clinical deployment, a large number of phage endolysins have been studied for their antibacterial potential against bacterial pathogens, including S. aureus. The present chapter provides a comprehensive account of the various endolysins, natural and engineered, studied as antimicrobial agents against drug resistant S. aureus.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"245-311"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-derived antimicrobial peptides (AMPs): Blue biotechnological assets for sustainable healthcare and circular bioeconomy.","authors":"Chandrabose Selvaraj, Deepali Desai, Sergio de Los Santos-Villalobos, Mani Jayaprakashvel, Radhakrishnan Muthezhilan, Sanjeev Kumar Singh","doi":"10.1016/bs.apcsb.2025.08.002","DOIUrl":"10.1016/bs.apcsb.2025.08.002","url":null,"abstract":"<p><p>The global antimicrobial resistance (AMR) crisis drives the demand for novel therapeutics, positioning marine-derived antimicrobial peptides (AMPs) as sustainable alternatives with unique structural and functional advantages. These cationic, amphipathic molecules, from the source of diverse marine organisms, such as invertebrates, extremophiles, and cyanobacteria, exhibit broad-spectrum activity against drug-resistant pathogens through mechanisms like membrane disruption and immunomodulation. Their low resistance propensity and multifunctional bioactivity (eg., antioxidant, antimicrobial, anticancer) underscore therapeutic potential beyond the conventional antibiotics. Advances in genomic and metagenomic tools, machine learning, and synthetic biology are revolutionizing AMP discovery, enabling targeted mining of marine biodiversity and peptide optimization for enhanced stability and specificity. Biotechnological innovations support scalable production through heterologous expression and marine biomass valorization, which aligns with the principles of the circular economy. Marine-sourced AMPs demonstrate transformative applications across various healthcare, aquaculture, food safety, and environmental remediation, that majorly reduce the dependence on synthetic chemicals. Their integration into blue bioeconomy frameworks is promoting sustainable bio-prospects, marine ecosystem conservation, and progress towards the United Nations Sustainable Development Goals. This review narrates the collective research and also addresses the critical challenges, including production scalability and regulatory frameworks, to outline a clear pathway for the marine sourced AMP commercialization. By bridging the antimicrobial innovation with circular biotechnology, marine-sourced AMPs are exemplifying the ocean's role as a reservoir of sustainable solutions for global health and bioeconomic resilience.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"171-201"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}