Advances in protein chemistry and structural biology最新文献

{"title":"Therapeutics immunotargets for Tauopathy.","authors":"Subashchandrabose Chinnathambi, Nagaraj Rangappa","doi":"10.1016/bs.apcsb.2025.10.015","DOIUrl":"10.1016/bs.apcsb.2025.10.015","url":null,"abstract":"<p><p>Alzheimer's disease is a multi-factor involved neurodegenerative disease. In Alzheimer's condition, the pathological protein transfer from cell to cell and cause other cells to degenerate, similar to prion like diseases, this pathological protein transfer is exacerbated by neuroinflammation, mitochondrial dysfunction, oxidative stress, autophagy impairment, and cholinergic deficits. Neuroinflammation, driven by chronic microglial activation, produces excessive cytokines that worsen Tau hyperphosphorylation. Mitochondrial dysfunction, characterized by impaired energy metabolism, enzyme deficits in the TCA cycle, and ROS overproduction, leads to oxidative damage to proteins, lipids, and nucleic acids. Oxidative stress further accelerates neuronal damage. Autophagy dysfunction, caused by impaired mTOR signalling, disrupts the clearance of Aβ and Tau, facilitating their accumulation. Additionally, cholinergic deficits, including reduced acetylcholine levels, impair cognitive functions like memory and learning. Therapeutic approaches targeting these interconnected mechanisms, such as modulating inflammation, restoring mitochondrial and autophagy functions, and addressing the amyloid and Tau pathways will offers promising directions for treating Alzheimer's disease by developing an effective intervention to manage this debilitating disorder.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"151 ","pages":"267-302"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939889","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":"Actin-associated growth cone of Tau and its intracellular localization.","authors":"Gowshika Velmurugan, Madhura Chandrashekar, Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2025.10.025","DOIUrl":"10.1016/bs.apcsb.2025.10.025","url":null,"abstract":"<p><p>Growth cones, the dynamic tips of extending axons, rely on intricate interactions between actin and microtubule cytoskeletal elements for their guidance behaviors. Central to this process is Tau, a microtubule-associated protein known for its role in stabilizing microtubules in neurons. Tau's additional function in regulating actin-microtubule interactions, crucial for neurite formation and growth cone pathfinding. Tau, along with other linker proteins, facilitates the crosslinking between microtubules and actin filaments, essential for the cohesive function of the cytoskeleton during axonal growth. Furthermore, Tau's responsiveness to external guidance cues underscores its significance in growth cone navigation. Knockdown experiments targeting Tau have revealed profound effects on microtubule protrusion, actin-microtubule organization, growth cone morphology, and axon pathfinding. This review highlights the intricate interplay between Tau and cytoskeletal dynamics, shedding light on its pivotal role in orchestrating growth cone guidance mechanisms.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"119-139"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571806","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":"Understanding the impact of cytoskeleton disruption on synaptic plasticity in Alzheimer's disease.","authors":"Basavaraju Kc, Poornima Priyadarshini","doi":"10.1016/bs.apcsb.2025.10.020","DOIUrl":"10.1016/bs.apcsb.2025.10.020","url":null,"abstract":"<p><p>Tau acetylation plays a critical role in the pathogenesis of Alzheimer's disease (AD) by disrupting cytoskeletal dynamics and synaptic plasticity. Acetylated tau aggregates contribute to the formation of neurofibrillary tangles (NFTs), leading to microtubule destabilization, impaired intracellular transport, and dysregulation of synaptic plasticity mechanisms. The cytoskeletal proteins, comprising microfilaments, microtubules, and intermediate filaments, are essential for maintaining neuronal structure, polarity, and signaling. The disruption of cytoskeletal integrity impairs dendritic spine formation, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor trafficking, mitochondrial transport, and autophagy, all crucial for synaptic plasticity. Glial cells, including astrocytes, oligodendrocytes, and microglia, also contribute to synaptic plasticity by interacting with neurons and regulating the extracellular environment. Acetylated tau aggregates interfere with these glial functions, exacerbating synaptic dysfunction. Moreover, cytoskeleton disruption impairs autophagy, mitochondrial dynamics, and function, leading to increased oxidative stress, reduced Adenosine triphosphate (ATP) production, and neuronal apoptosis. The accumulation of dysfunctional mitochondria further contributes to synaptic impairment and cognitive decline in AD. Understanding the complex interplay between tau acetylation, cytoskeletal dynamics, and synaptic plasticity is crucial for developing targeted therapeutic interventions to mitigate the progression of AD and other tauopathies.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"150 ","pages":"285-318"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571776","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":"Understanding molecular role of lipids for Alzheimer's disease.","authors":"Riddhi Upadhyay, Gowshika Velmurugan, Deena Krishnan, R Sivasamy, Murugan Sevanan, Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2025.10.011","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2025.10.011","url":null,"abstract":"<p><p>Human health and neurological functions are significantly impacted by lipids, the fundamental building block of cell membranes. The central nervous system is rich in lipids, and they are evidently disturbed in neurological conditions and neurodegenerative diseases like Alzheimer's disease (AD). Alteration in lipid profile is highly linked with aging. During early onset of AD, there is a noted lipid peroxidation and modifications of fatty acids at the level of lipid rafts in the neuronal cells. AD is an age-linked neurodegenerative condition with multifaceted etiology, with combining genetic and environmental risk factors, which lacks disease-modifying therapies. While the aberrant deposition of lipids was shown in the initial studies of AD neuropathology. Clinically, lipidomic and metabolomic research have constantly exposed the changes in the levels of various lipid classes emerging in early onset of AD individuals. Also, decades of investigations have discovered multifactorial link between lipid metabolism and key AD pathogenic pathway such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Herewith, we highlighted the features that impact lipid composition in neuronal cells, and the association of different lipids with known aspects of AD pathogenesis, and potential therapeutics that aim lipid crossroads.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"153 ","pages":"191-210"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443867","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":"Identification of common hub genes and pathways in systemic lupus erythematosus and cervical cancer using bioinformatics approach.","authors":"Tamizhini Loganathan, S Madhulekha, Hatem Zayed, George Priya Doss C","doi":"10.1016/bs.apcsb.2025.10.009","DOIUrl":"10.1016/bs.apcsb.2025.10.009","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complex autoimmune condition characterized by multifactorial pathogenesis involving dysregulated immune responses. It has been associated with an elevated risk of various cancers, notably cervical cancer (CC), one of the most common cancers in women globally. Despite this association, the molecular mechanisms linking SLE and CC remain incompletely defined. To investigate this intersection, we employed integrative bioinformatics approaches to analyze transcriptomic datasets relevant to both SLE and CC, including GSE112087, GSE154851, GSE46907, GSE49454, GSE50772, GSE63514, GSE64217, GSE63678, GSE7803, and GSE9750 . We performed differential gene expression analysis, constructed Protein-Protein Interaction (PPI) networks, and carried out functional annotation to pinpoint pivotal hub genes and signaling pathways implicated in both diseases. Our analysis revealed significant differentially expressed genes (DEGs) in SLE, predominantly associated with cytokine and interferon alpha/beta signaling pathways, as well as the innate immune response. Notable hub genes included MX1, ISG15, and STAT1. In CC, DEGs were chiefly enriched in the mitotic cell cycle and cytokine signaling processes, with CDK1 and DLGAP5 standing out as key hub genes. The cross-disease analysis identified shared DEGs between SLE and CC, particularly in the interferon-alpha/beta and cytokine signaling pathways. This suggests a shared molecular architecture that underlies both autoimmune and cancer pathogenesis. Our study underscores the common molecular pathways between SLE and CC, highlighting the significance of interferon and cytokine signaling in the pathogenesis of both diseases. These insights set the stage for future research into potential therapeutic targets for the treatment of both SLE and CC.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"152 ","pages":"103-121"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004473","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 properties of plant-based proteins for alternative protein.","authors":"Anamika Das, Avra Sau, Santosh Chokkakula, Prakash Ramalingam, S Subhashini, Balasubramani Ravindran, D S Prabakaran","doi":"10.1016/bs.apcsb.2026.08.012","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.08.012","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Alternative proteins, or alt proteins, are proteins obtained from non-animal sources like plant sources, meat cultured in labs, and other sources like fungi and insects. These contain a variety of benefits and are gaining popularity worldwide. Some chronic diseases require a low-red-meat diet, which can be fulfilled through alternative proteins, providing similar benefits to those of animal-based proteins. This chapter deals with the sustainability aspect of using alternative proteins. A sustainable protein refers to a protein that is efficient in terms of health benefits, taste, environmental impact, affordability, etc., which makes it sustainable in the market, i.e., being able to be used for a long time without depleting any resources. This sustainability aspect makes them an attractive option for addressing global food security challenges. There are several health and nutrient benefits of alternative proteins over the traditional methods. Traditional proteins raise a lot of concerns like greenhouse gas emissions, animal welfare, and vulnerability to diseases and antibiotic resistance. From the production, where less land, water, and soil are being used, to the nutrient values that can be fortified based on the requirements, this possesses the properties of a high-value-added product. The sustainability of the product can be tested through life impact assessment, where the complete process from scratch is analyzed to come to the conclusion about its environmental footprint. Consumers today appeal to the taste factor, health factor, source of the protein, etc. There are lots of cultures and ethnicities where the use of alternative proteins is being done on a regular basis, for example, the consumption of insects in Southeast Asia as a part of celebration, the consumption of legumes in South Asian countries, etc., where the market for this is better. Also, with trending veganism and many people switching to plant-based products, the consumer impact is growing day by day, which is also analyzed with surveys and case studies in this chapter with respect to alternative proteins. Today's population growth and climatic changes exert great pressure on traditional methods to sustain the varying environmental conditions and maintain food security. This can be overcome through the means of alternative proteins that use late technologies such as high-pressure processing (HPP), pulse electric field (PEF) technology, precision fermentation, and 3D printing, which not only improve the food quality but also provide efficient production, adding to the economy. Further, the chapter also addresses issues such as socio-economic sustainability and global initiatives that have been taken or have to be taken and about animal welfare, as animal slaughtering is not involved. Despite having all these advantages, this might still possess some challenges, such as consumer acceptance, cost competitiveness, regulatory barriers, market competition, supply chain comple","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"154 ","pages":"33-72"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007594","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":"Nutritional and functional properties of alternative proteins.","authors":"P Amudha, R Muthuvel, Dapkupar Wankhar, Gowtham Kumar Subbaraj, G R Gunassekaran","doi":"10.1016/bs.apcsb.2026.08.018","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.08.018","url":null,"abstract":"<p><p>As the size of the human population increases, shortage of essential proteinaceous food products paved the way to found for new, sustainable, and natural protein resources from insects, legume crops, terrestrial and aquatic weeds, and fungi. Due to the rich source of essential amino acids, fatty acids and trace elements, Insect proteins play an important role in the production of alternative proteins. Unconventional legume crops were found to be rich in phytochemical, nutritional, and therapeutic properties, shows excellent properties to withstand extreme environmental condition. This article comprises the recent status of underutilized legume crops, algae, fungi, and insects are used as alternative protein sources, for the production protein rich foods products, including food formulations and functional characteristics features of alternative plant-based proteins and edible insect proteins as novel foods products. Production of alternative protein increases by exploring increased protein quality, advanced processing technology, and large-scale application in the food and industrial sectors. Overall, alternative protein found to play an important role in developing a sustainable food culture, incorporating nutritional safety, and reducing the environmental effects of conventional protein production.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"154 ","pages":"567-592"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007637","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":"Fungal proteins as eco-friendly alternate proteins.","authors":"Radha Vijayaraj, Kareem Altaff, Periyasamy Vijayalakshmi, T Mowna Sundari, Deepali Desai","doi":"10.1016/bs.apcsb.2026.08.016","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.08.016","url":null,"abstract":"<p><p>The rapid growth of the global population and the increasing demand for nutritious food have created an urgent need to identify sustainable and environmentally friendly protein sources. Traditionally, animal-based foods such as meat, fish, eggs, and dairy products have been the primary sources of dietary protein. However, large-scale livestock production is associated with significant environmental challenges, including greenhouse gas emissions, extensive land and water use, and biodiversity loss. These issues raise concerns about the long-term sustainability of conventional animal protein production. Although plant-based proteins contribute significantly to global protein intake, limitations remain regarding protein quality, essential amino acid composition, and the substantial agricultural resources required for large-scale crop production. Consequently, there is growing interest in exploring alternative protein sources that are nutritionally adequate, environmentally sustainable, and economically viable. Fungal proteins have emerged as promising alternatives due to their high nutritional value and lower environmental footprint. Among them, mycoprotein produced through the fermentation of the filamentous fungus Fusarium venenatum represents one of the most successful commercially developed fungal protein products. Mycoprotein is rich in high-quality protein, dietary fiber, essential amino acids, and important micronutrients, while being naturally low in fat and free from cholesterol. Furthermore, mycoprotein production requires fewer natural resources and generates lower environmental impacts compared with conventional livestock systems. Hence, this chapter highlights fungal proteins as eco-friendly alternative protein sources, discussing their nutritional composition, production technologies, environmental benefits, and potential applications in food and feed industries.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"154 ","pages":"203-256"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007769","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 inhibit Tau aggregation and modulates its pathology.","authors":"Subashchandrabose Chinnathambi, Nagaraj Rangappa, Sneha Malik","doi":"10.1016/bs.apcsb.2025.09.002","DOIUrl":"10.1016/bs.apcsb.2025.09.002","url":null,"abstract":"<p><p>Alzheimer's disease is mainly caused by two proteins, Tau and Amyloid-β. While there are several cures currently being explored for it, there is no cure yet for the disease progression and prevention, but only those to alleviate the symptoms. One of the hypothesis for the cause of the Alzheimer's disease is the microbial hypothesis. This suggests that there are a lot of microorganisms present in our body which can contribute to the disease pathology by leading to symptoms such as neuroinflammation. Our body has certain molecules to maintain innate immunity, known as antimicrobial peptides. Recently, several studies suggest the roles of these molecules in the Alzheimer's disease as therapeutic molecules and as biomarkers. Amyloid beta which is one of the major proteins is suggested to be an antimicrobial peptide on its own. The formation of its oligomers and plaques is due to neuroprotective reasons. A similar theory exists for the formation of neurofibrillary tangles (NFTs) from Tau. There include lactoferrin, LL-37 and defensins. They are often found in association with the aggregated proteins, amyloid beta and Tau. Additionally, fluctuations in their levels are often observed in several fluids and regions inside in patients with AD compared to the control cohorts. While their therapeutic potential has been proven, their mechanisms of action, effectivity and expedition towards clinical studies is yet to be done.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"149 ","pages":"375-394"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045822","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":"Cross-cancer transcriptomic integration identifies a core immune-signaling network in hormone-driven malignancies.","authors":"Prasanna Kumar Selvam, Supraja Mohan, Karthick Vasudevan","doi":"10.1016/bs.apcsb.2026.04.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2026.04.002","url":null,"abstract":"<p><p>Hormone-dependent malignancies, including breast, ovarian, thyroid, and prostate cancers, are driven by dysregulated endocrine signaling but exhibit marked heterogeneity in molecular architecture and therapeutic response. Whether these cancers share conserved transcriptional programs that transcend tissue-of-origin remains incompletely understood. In this study, we applied a systematic, direction-aware transcriptomic framework to identify shared gene expression signatures across hormone-driven malignancies using RNA-sequencing data with matched non-malignant controls. Differential expression analysis was performed independently for each cancer type using DESeq2, identifying 15,648 significant differentially expressed genes (DEGs). Integration of DEGs across cancers using a presence-direction matrix revealed limited universal overlap, with only one gene shared across all four cancers. Leave-one-out sensitivity analysis demonstrated that prostate cancer exhibited reduced transcriptional concordance relative to other malignancies. Exclusion of prostate cancer resulted in the highest overlap and direction-consistent dysregulation, identifying 10,948 shared DEGs across breast, ovarian, and thyroid cancers, including 1043 genes with consistent regulatory direction. Restriction to genes common to all three retained cancers defined a core pan-hormone transcriptional signature comprising 270 genes. These genes were prioritized using a composite statistical score integrating mean absolute log2 fold change and Fisher-combined adjusted p-values across cancers. Functional enrichment analysis of the top 100 ranked genes using g:Profiler revealed significant enrichment of immune-related biological processes, cytokine signaling, membrane-associated signal transduction, and protein-protein interaction functions. Collectively, this study identifies a conserved immune-signaling-centric transcriptional program shared across breast, ovarian, and thyroid cancers.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"153 ","pages":"77-94"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443887","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}