Biochemical Society transactions最新文献

How does protein aggregate structure affect mechanisms of disaggregation? 蛋白质聚集结构如何影响分解机制？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-23 DOI: 10.1042/BST20253077

YuChen Yang, Hays S Rye

{"title":"How does protein aggregate structure affect mechanisms of disaggregation?","authors":"YuChen Yang, Hays S Rye","doi":"10.1042/BST20253077","DOIUrl":"https://doi.org/10.1042/BST20253077","url":null,"abstract":"Protein misfolding and aggregation underpin numerous pathological conditions, including Alzheimer's, Parkinson's, and Huntington's diseases. Within cells, the competition between protein folding and misfolding- driven aggregation necessitates intricate quality control systems known collectively as the proteostasis network, with molecular chaperones playing central roles. Critical gaps remain in our understanding of why certain protein aggregates are amenable to efficient chaperone-mediated disassembly, while others resist such intervention. Aggregates can be most broadly categorized into structurally ordered amyloid fibrils and more irregular amorphous clusters. Amyloid fibrils are characterized by a highly structured, cross-β-sheet architecture, and they generally display nucleation-driven growth kinetics. In contrast, amorphous aggregates form through heterogeneous interactions among partially unfolded proteins, which typically lack ordered and repeating structure but still display poorly understood, specific assembly constraints. Importantly, amorphous aggregation and amyloid formation are often linked to one another, with several different types of aggregate structures forming at the same time. The ability of molecular chaperones to remodel and disassemble aggregates is affected by aggregate size, internal structure, surface dynamics, and exposure of chaperone-binding sites. However, despite these insights, the mechanistic complexity, aggregate heterogeneity, and dynamic properties present substantial experimental and theoretical challenges. Addressing these challenges will require innovative approaches combining single-molecule biophysics, structural biology, and computational modeling to unveil universal principles governing protein aggregation and disaggregation within cellular environments.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706128","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}

引用次数: 0

Advances in mechanochemical modelling of vertebrate gastrulation. 脊椎动物原肠形成的力学化学模型研究进展。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-22 DOI: 10.1042/BST20240469

Alex M Plum, Mattia Serra, Cornelis J Weijer

{"title":"Advances in mechanochemical modelling of vertebrate gastrulation.","authors":"Alex M Plum, Mattia Serra, Cornelis J Weijer","doi":"10.1042/BST20240469","DOIUrl":"https://doi.org/10.1042/BST20240469","url":null,"abstract":"Gastrulation is an essential process in the early embryonic development of all higher animals. During gastrulation, the three embryonic germ layers, the ectoderm, mesoderm and endoderm, form and move to their correct positions in the developing embryo. This process requires the integration of cell division, differentiation and movement of thousands of cells. These cell behaviours are coordinated through shortand long-range signalling and must involve feedback to execute gastrulation in a reproducible and robust manner. Mechanosensitive signalling pathways and processes are being uncovered, revealing that shortand long-range mechanical stresses integrate cell behaviours at the tissue and organism scale. Because the interactions between cell behaviours, signalling and feedback are complex, combining experimental and modelling approaches is necessary to elucidate the regulatory mechanisms that drive development. We highlight how recent experimental and theoretical studies provided key insights into mechanical feedback that coordinates relevant cell behaviours at the organism scale during gastrulation. We outline advances in modelling the mechanochemical processes controlling primitive streak formation in the early avian embryo and discuss future developments.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697468","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}

引用次数: 0

Why are imprints unstable in pluripotent stem cells? 为什么印迹在多能干细胞中不稳定？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20243003

Maria Arez, Simão Teixeira da Rocha

{"title":"Why are imprints unstable in pluripotent stem cells?","authors":"Maria Arez, Simão Teixeira da Rocha","doi":"10.1042/BST20243003","DOIUrl":"https://doi.org/10.1042/BST20243003","url":null,"abstract":"Pluripotent stem cells (PSCs) possess the remarkable ability to self-renew and differentiate into nearly any cell type, making them invaluable for both research and therapeutic applications. Despite these powerful attributes, PSCs are vulnerable to genetic and epigenetic instabilities that can undermine their reliability and safety. While genetic abnormalities can be routinely monitored with established guidelines, epigenetic instabilities often go unchecked. Among the most recurrent epigenetic defects in PSCs are errors in genomic imprinting - a process that governs parent-of-origin-specific monoallelic expression of certain genes through differential marking of the two parental alleles by DNA methylation. When disrupted, it becomes a source of a dozen developmental conditions known as imprinting diseases. In PSCs, once imprinting errors arise, they remain throughout cellular differentiation, casting uncertainty over the use of PSC-derived cells for disease modelling and regenerative medicine. In this review, we provide an overview of imprinting defects in both mouse and human PSCs, delving into their origins and consequences. We also discuss potential correction strategies that aim to enhance imprinting stability, ultimately paving the way for safer, more reliable PSC use in research and clinical applications.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658203","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}

引用次数: 0

Progress in recapitulating morphogenesis of blood microvascular structures for microphysiological systems development. 微生理系统发育中血液微血管结构形态发生概述的研究进展。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20240572

Ana Ximena Monroy-Romero, Mathieu Hautefeuille

{"title":"Progress in recapitulating morphogenesis of blood microvascular structures for microphysiological systems development.","authors":"Ana Ximena Monroy-Romero, Mathieu Hautefeuille","doi":"10.1042/BST20240572","DOIUrl":"https://doi.org/10.1042/BST20240572","url":null,"abstract":"Microphysiological systems (MPSs) are complex cell culture platforms, designed to closely replicate the cellular microenvironment of tissues under physiopathological conditions. A critical aspect of these systems is the integration of a vascular network, which facilitates nutrient exchange, supports heterotypic cell interactions, and increases culture viability. A top-down engineering approach, where a prefabricated scaffold is used to introduce endothelial cells, has been widely employed. However, promoting self-organization through a bottom-up paradigm has proven more effective in recapitulating the geometric features of microvasculature, particularly the network nature of it as the capillary diameters. In vivo vasculature formation occurs primarily through two self-organization processes: vasculogenesis and angiogenesis. These processes follow a series of co-ordinated and regulated steps, driven by microenvironmental cues such as cell identity and heterogeneity, soluble factor distribution, extracellular matrix composition and mechanics, and flow-induced mechanical strains. By incorporating these parameters into in vitro platforms, researchers can develop physiologically relevant vascularized MPS for applications in drug development and disease modeling. This review explores the key mechanisms underlying vascular self-organization and highlights how they are being integrated into tissue-specific MPS platforms to achieve vascularization, which enhances the potential of MPS for studying various physiological and pathological processes.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658269","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}

引用次数: 0

The fantastic voyage: primordial germ cell migration through the developing mouse embryo. 奇妙的旅程：原始生殖细胞通过发育中的小鼠胚胎迁移。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-17 DOI: 10.1042/BST20253009

Katharine Goodwin

引用次数: 0

UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential. UBQLN2在神经退行性疾病中的作用机制和新出现的治疗潜力

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-14 DOI: 10.1042/BST20253053

Autumn M Matthews, Alexandra M Whiteley

{"title":"UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.","authors":"Autumn M Matthews, Alexandra M Whiteley","doi":"10.1042/BST20253053","DOIUrl":"https://doi.org/10.1042/BST20253053","url":null,"abstract":"Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly expressed in the nervous system and muscle tissue and has been linked to multiple neurodegenerative diseases. In particular, point mutations of UBQLN2 cause an X-linked, dominant form of amyotrophic lateral sclerosis (ALS), ALS with frontotemporal dementia (ALS/FTD), or FTD. Failed protein degradation is a hallmark of many neurodegenerative diseases, including ALS and FTD; however, it is not clear exactly how ALS/FTD-associated UBQLN2 mutations contribute to pathogenesis. Recent studies have revealed the complexity of UBQLN2 biology and allow deeper understanding as to how UBQLN2 dysfunction may contribute to neurodegenerative disease. UBQLN2 is necessary for mitochondrial protein degradation and for regulating mitochondrial turnover, both of which are essential for motor neurons and have been implicated in the pathogenesis of ALS. Stress granule (SG) formation and regulation are also affected by UBQLN2 mutations, and their dysregulation may contribute to the toxic protein aggregation and SG changes observed in neurodegenerative disease. Finally, there are compelling links connecting UBQLN2 dysfunction with changes to downstream neuronal morphology, function, and behavior. This review will detail the emerging consensus on how UBQLN2 protects against neurodegenerative disease and will provide insights into potential therapeutic approaches.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641650","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}

引用次数: 0

DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases. digg - dubs：人类和病毒交叉反应性泛素蛋白酶解ISG15的机制和功能。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-09 DOI: 10.1042/BST20240859

Thomas Bonacci, Michael J Emanuele

引用次数: 0

Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2. ACE2和TMPRSS2在健康人及SARS-CoV-2患者中的影响及调控

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-08 DOI: 10.1042/BST20241052

Marie Lykke Bach, Boye L Jensen

{"title":"Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.","authors":"Marie Lykke Bach, Boye L Jensen","doi":"10.1042/BST20241052","DOIUrl":"https://doi.org/10.1042/BST20241052","url":null,"abstract":"The present narrative review focuses on organ distribution, co-localization, age-, and sex-dependent changes in angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) and how such changes associate with SARS-CoV-2 virus entry and disease severity in humans. ACE2 is a membrane-bound enzyme with lower abundance in children/young adults compared with elderly, with no protein abundance difference between ages 35-50 and >80 but higher in females at reproductive age. ACE2 locates predominantly in gastrointestinal (GI)-tract epithelia, kidney proximal tubules, male and female reproductive organs with very low levels in the lungs. Estrogen upregulates ACE2, which can be shed from cells into plasma by, for example ADAM17, while remaining active. TMPRSS2 is a membrane-associated serine protease with androgen dependence. The highest levels in humans are found in male reproductive organs, kidney, and GI-tract. Co-localization with ACE2 in alveolar type 2 cells is based mostly on in vitro studies. Documentation of clustering of ACE2 and TMPRSS2 in human tissues is scarce and best in oral-pharyngeal mucosa. In patients with mild-to-serious COVID-19 disease, there is no consistent change in circulating renin, aldosterone, ACE and ACE2 activities, angiotensin II (ANGII), and Ang1-7. Increased ANGII levels are reported in critically ill patients, while ACE2 is massively present in urine. Use of RAAS inhibitors is not associated with negative outcomes in patients with COVID-19. In conclusion, co-localization of ACE2 and TMPRSS2 in oral and airway epithelia may explain the primary route of infection for SARS-CoV-2 virus. Higher risk for serious disease in elderly males may not be accounted for by quantitative changes in the proteins.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590351","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}

引用次数: 0

The rise of AMPylation: from bacterial beginnings to modern implications in health and disease. ampyation的兴起：从细菌起源到健康和疾病的现代含义。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-08 DOI: 10.1042/BST20253056

Meghomukta Mukherjee, Anju Sreelatha

引用次数: 0

Computational modelling of aggressive B-cell lymphoma. 侵袭性b细胞淋巴瘤的计算模型。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-04 DOI: 10.1042/BST20253039

Eleanor S Jayawant, Aimilia Vareli, Andrea Pepper, Chris Pepper, Fabio Simoes, Simon Mitchell

{"title":"Computational modelling of aggressive B-cell lymphoma.","authors":"Eleanor S Jayawant, Aimilia Vareli, Andrea Pepper, Chris Pepper, Fabio Simoes, Simon Mitchell","doi":"10.1042/BST20253039","DOIUrl":"https://doi.org/10.1042/BST20253039","url":null,"abstract":"Decades of research into the molecular signalling determinants of B cell fates, and recent progress in characterising the genetic drivers of lymphoma, has led to a detailed understanding of B cell malignancies but also revealed daunting heterogeneity. While current therapies for diffuse large B-cell lymphoma are effective for some patients, they are largely agnostic to the biology of each individual's disease, and approximately one third of patients experience relapsed/refractory disease. Consequently, the challenge is to understand how each patient's mutational burden and tumour microenvironment combine to determine their response to treatment; overcoming this challenge will improve outcomes in lymphoma. This mini review highlights how data-driven modelling, statistical approaches and machine learning are being used to unravel the heterogeneity of lymphoma. We review how mechanistic computational models provide a framework to embed patient data within knowledge of signalling. Focusing on recurrently dysregulated signalling networks in lymphoma (including NF-κB, apoptosis and the cell cycle), we discuss the application of state-of-the-art mechanistic models to lymphoma. We review recent advances in which computational models have demonstrated the power to predict prognosis, identify promising combination therapies and develop digital twins that can recapitulate clinical trial results. With the future of treatment for lymphoma poised to transition from one-size-fits-all towards personalised therapies, computational models are well-placed to identify the right treatments to the right patients, improving outcomes for all lymphoma patients.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558917","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}

引用次数: 0