FEBS Letters最新文献_第5页

Crystal structure of a family II pyrophosphatase from Thermodesulfobacterium commune and factors enabling its high-temperature adaptation 热脱硫菌群落II族焦磷酸酶的晶体结构及其高温适应因子

IF 3 4区生物学

FEBS Letters Pub Date : 2025-07-26 DOI: 10.1002/1873-3468.70124

Saki Maruoka, Takamasa Teramoto, Keiichi Watanabe, Yoshimitsu Kakuta

引用次数: 0

Aβ42 promotes the aggregation of α-synuclein splice isoforms via heterogeneous nucleation. a - β42通过异相成核促进α-突触核蛋白剪接异构体的聚集。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-07-26 DOI: 10.1002/1873-3468.70118

Alexander Röntgen, Zenon Toprakcioglu, Michele Vendruscolo

{"title":"Aβ42 promotes the aggregation of α-synuclein splice isoforms via heterogeneous nucleation.","authors":"Alexander Röntgen, Zenon Toprakcioglu, Michele Vendruscolo","doi":"10.1002/1873-3468.70118","DOIUrl":"https://doi.org/10.1002/1873-3468.70118","url":null,"abstract":"Increasing evidence suggests that amyloid-β (Aβ) and α-synuclein (αSyn) co-aggregate in Alzheimer's disease (AD) and Parkinson's disease (PD), an in other neurodegenerative disorders. We investigated how Aβ42 - the predominant Aβ form in AD - co-aggregates with four αSyn splice isoforms (αSyn-140, αSyn-126, αSyn-112 and αSyn-98) implicated in PD, finding evidence of a two-step process. Aβ42 first aggregated into fibrillar assemblies, which then acted as potent nucleation surfaces for initiating the aggregation of αSyn isoforms. Furthermore, pre-formed Aβ42 seeds promoted αSyn aggregation more strongly than in situ Aβ42 aggregates. Our results reveal a unified Aβ-αSyn co-aggregation mechanism, where Aβ aggregation and αSyn splicing synergistically drive co-deposition. These findings could help develop therapeutic tools to target key steps in disease-related co-aggregation pathways. Impact statement By demonstrating that Aβ42 fibril seeds serve as potent heterogeneous nucleation surfaces for four common α-synuclein splice isoforms, this study mechanistically links protein aggregation in Alzheimer's and Parkinson's diseases. Kinetic analysis identifies early cross-seeding events, suggesting intervention points to delay mixed amyloid pathologies in neurodegeneration.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717809","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}

引用次数: 0

Archaeal protein containing domain of unknown function 2193 undergoes oligomeric reconfiguration upon iron–sulfur cluster binding 含未知功能结构域2193的古细菌蛋白在铁-硫簇结合后发生寡聚重组。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-07-26 DOI: 10.1002/1873-3468.70120

Emily M. Dieter, James Larson, Monika Tokmina-Lukaszewska, Jin Xiong, Jared Green, Yisong Guo, William E. Broderick, Brian Bothner, Joan B. Broderick

引用次数: 0

Redox-dependent binding and conformational equilibria govern the fluorescence decay of NAD(P)H in living cells. 氧化还原依赖的结合和构象平衡控制着活细胞中NAD(P)H的荧光衰减。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-07-25 DOI: 10.1002/1873-3468.70125

Thomas S Blacker, Nimit Mistry, Nicoletta Plotegher, Elizabeth R Westbrook, Michael D E Sewell, John Carroll, Gyorgy Szabadkai, Angus J Bain, Michael R Duchen

引用次数: 0

TRAF2 binds to TIFA via a novel motif and contributes to its autophagic degradation. TRAF2通过一个新的基序与TIFA结合，并有助于其自噬降解。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-07-22 DOI: 10.1002/1873-3468.70110

Tom Snelling, Kodi Hunter, Celest W S Tay, Nicola T Wood, Philip Cohen

引用次数: 0

The 3' end of the tale-neglected isoforms in cancer. 癌症中被忽视的同工异构体的3'端。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-07-22 DOI: 10.1002/1873-3468.70122

Didem Naz Dioken, Ibrahim Ozgul, Ayse Elif Erson-Bensan

{"title":"The 3' end of the tale-neglected isoforms in cancer.","authors":"Didem Naz Dioken, Ibrahim Ozgul, Ayse Elif Erson-Bensan","doi":"10.1002/1873-3468.70122","DOIUrl":"https://doi.org/10.1002/1873-3468.70122","url":null,"abstract":"The evolutionary expansion of 3' untranslated regions (3'UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3'UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA-binding proteins and non-coding RNAs, thereby contributing to cell-type-specific and context-dependent gene expression. Mounting evidence highlights the importance of non-coding regions, particularly 3'UTRs, in normal physiology and disease states, including cancer. Genomic alterations and driver mutations in coding regions play a well-established role in cancer biology. Advances in long-read sequencing and 3'UTR-focused genome-/transcriptome-wide association studies (GWAS/TWAS) improve our understanding of transcriptome complexity and how mRNA isoforms with different 3'-ends may impact protein functions. This Review explores the regulatory roles of 3'UTRs, sources of 3'UTR isoform diversity, and implications in cancer, emphasizing the need for further research into their diagnostic and therapeutic potential. Impact statement This review highlights how alternative polyadenylation generates diverse mRNA 3'-end isoforms in cancer. Isoforms with distinct 3'UTRs are differentially regulated by microRNAs and RNA-binding proteins, while intronically polyadenylated isoforms can lead to C-terminally truncated proteins with altered functions.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689670","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}

引用次数: 0

Detyrosinated α-tubulin mediates mitochondrial dysfunction and diastolic impairment in heart failure with preserved ejection fraction 脱氨酸α-微管蛋白介导射血分数保留心衰患者线粒体功能障碍和舒张功能损害。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-07-22 DOI: 10.1002/1873-3468.70119

Shunsuke Miura, Tomofumi Misaka, Toranosuke Sekine, Ryo Ogawara, Shohei Ichimura, Yusuke Tomita, Tetsuro Yokokawa, Masayoshi Oikawa, Takafumi Ishida, Yasuchika Takeishi

{"title":"Detyrosinated α-tubulin mediates mitochondrial dysfunction and diastolic impairment in heart failure with preserved ejection fraction","authors":"Shunsuke Miura, Tomofumi Misaka, Toranosuke Sekine, Ryo Ogawara, Shohei Ichimura, Yusuke Tomita, Tetsuro Yokokawa, Masayoshi Oikawa, Takafumi Ishida, Yasuchika Takeishi","doi":"10.1002/1873-3468.70119","DOIUrl":"10.1002/1873-3468.70119","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, yet its molecular basis remains unclear. Here, we identified detyrosinated α-tubulin as a key cause of mitochondrial dysfunction and impaired mitophagy in HFpEF. In a SAUNA-induced HFpEF mouse model, elevated vasohibin-1 (VASH1) expression was associated with increased detyrosinated α-tubulin. In H9c2 cardiomyocytes, VASH1 overexpression or tubulin tyrosine ligase knockout raised detyrosinated α-tubulin levels, leading to reduced mitochondrial respiration. Detyrosinated α-tubulin on mitochondria impaired Parkin recruitment and polyubiquitination of voltage-dependent anion channel 1, suppressing mitophagy. Cardiac-specific VASH1 expression recapitulated HFpEF-like phenotypes, including diastolic dysfunction, reduced exercise capacity, and decreased mitochondrial complex activity. These findings suggest that α-tubulin detyrosination contributes to HFpEF pathogenesis and may serve as a therapeutic target.\u0000 ","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 17","pages":"2474-2490"},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948139","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}

引用次数: 0

ERBIN limits epithelial cell plasticity via suppression of TGF-β signaling. ERBIN通过抑制TGF-β信号传导限制上皮细胞的可塑性。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-07-20 DOI: 10.1002/1873-3468.70121

Chao Li, Gerard van der Zon, Peter Ten Dijke, Tong Shen

引用次数: 0

The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases. 上皮屏障理论为过敏性疾病和其他慢性非传染性疾病的起源提供了一个全面的解释。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-07-18 DOI: 10.1002/1873-3468.70113

Can Zeyneloglu, Huseyn Babayev, Ismail Ogulur, Sena Ardicli, Yagiz Pat, Duygu Yazici, Bingjie Zhao, Lihong Chang, Xiaoqing Liu, Paolo D'Avino, Manru Li, Ceren Biçer, Fatma Hacer Kurtoğlu Babayev, Raja Dhir, Kari C Nadeau, Marie-Charlotte Brüggen, Mubeccel Akdis, Cezmi A Akdis

{"title":"The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases.","authors":"Can Zeyneloglu, Huseyn Babayev, Ismail Ogulur, Sena Ardicli, Yagiz Pat, Duygu Yazici, Bingjie Zhao, Lihong Chang, Xiaoqing Liu, Paolo D'Avino, Manru Li, Ceren Biçer, Fatma Hacer Kurtoğlu Babayev, Raja Dhir, Kari C Nadeau, Marie-Charlotte Brüggen, Mubeccel Akdis, Cezmi A Akdis","doi":"10.1002/1873-3468.70113","DOIUrl":"https://doi.org/10.1002/1873-3468.70113","url":null,"abstract":"The epithelial barrier theory proposes that modern environmental exposures compromise skin and mucosal surfaces, initiating local inflammation that propagates systemically. The theory integrates epidemiological trends, molecular mechanistic data, and emerging clinical data to show how everyday exposures cause the development and exacerbation of more than 70 chronic noncommunicable diseases. A canonical epithelial cell and barrier injury cascade takes place, generating oxidative stress with increased reactive oxygen species, the release of alarmins, and multiple chemokines and epithelial barrier disruption. The damage to epithelial barriers occurs together with microbial dysbiosis. The alerted immune system fuels various immune activation loops involving multiple cells and chemokines and links barrier leakiness to atopic, autoimmune, metabolic, and neuropsychiatric disease clusters. Supporting the one health concept, abundant exposure of domestic animals and pets to the same groups of toxic substances related to their diseases has recently become more evident. The prevalence of these preventable diseases showed an increase in parallel to industrialization and modernization and epidemiologic exposure to culprit substances throughout the whole world, with a substantial public health burden reaching trillions of dollars each year. Impact statement Modern environmental exposures compromise epithelial barriers, triggering inflammation, microbial dysbiosis, and chronic disease clusters-atopic, autoimmune, metabolic, neuropsychiatric. These preventable conditions now affect millions and impose a public health and economic burden of trillions annually in healthcare costs and lost productivity.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658804","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}

引用次数: 0

From omics to AI-mapping the pathogenic pathways in type 2 diabetes. 从组学到人工智能绘制2型糖尿病的致病途径。

IF 3.5 4区生物学

FEBS Letters Pub Date : 2025-07-17 DOI: 10.1002/1873-3468.70115

Siobhán O'Sullivan, Lu Qi, Pierre Zalloua

{"title":"From omics to AI-mapping the pathogenic pathways in type 2 diabetes.","authors":"Siobhán O'Sullivan, Lu Qi, Pierre Zalloua","doi":"10.1002/1873-3468.70115","DOIUrl":"https://doi.org/10.1002/1873-3468.70115","url":null,"abstract":"Understanding the biochemical pathways and interorgan cross talk underlying type 2 diabetes (T2D) is essential for elucidating its pathophysiology. These pathways provide a mechanistic framework linking molecular dysfunction to clinical phenotypes, enabling patient stratification based on dominant metabolic disturbances. Advances in multi-omics, including genomics, transcriptomics, proteomics, microbiomics, and metabolomics, offer a systems-level view connecting genetic variants and regulatory elements to disease traits. Single-cell technologies further refine this perspective by identifying cell-type-specific drivers of β-cell failure, hepatic glucose dysregulation, and adipose inflammation. AI-driven analytics and machine learning integrate these high-dimensional datasets, uncovering molecular signatures and regulatory networks involved in insulin signaling, lipid metabolism, mitochondrial function, and immune-metabolic cross talk. This review synthesizes current evidence on T2D's molecular architecture, emphasizing key pathways such as PI3K-Akt, AMPK, mTOR, JNK, and sirtuins. It also explores the role of gut microbiota in modulating host metabolism and inflammation. Adopting a pathway-centric systems biology approach moves beyond statistical associations toward mechanistic insight. Integrating multi-omics with AI-based modeling represents a transformative strategy for stratifying patients and guiding precision therapies in diabetes care. Impact statement This review translates complex biochemical pathways into therapeutic direction for type 2 diabetes, addressing a critical gap between molecular research and clinical care. By integrating multi-omics, AI, and systems biology, it empowers the scientific community to develop targeted interventions that reduce the global burden of this escalating metabolic disease.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648931","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}

引用次数: 0