Cell Chemical Biology最新文献

SynPull: An advanced method for studying neurodegeneration-related aggregates in synaptosomes using super-resolution microscopy

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-24 DOI: 10.1016/j.chembiol.2025.01.001

Shekhar Kedia, Emre Fertan, Yunzhao Wu, Yu P. Zhang, Georg Meisl, Jeff Y.L. Lam, Frances K. Wiseman, William A. McEwan, Annelies Quaegebeur, Maria Grazia Spillantini, John S.H. Danial, David Klenerman

{"title":"SynPull: An advanced method for studying neurodegeneration-related aggregates in synaptosomes using super-resolution microscopy","authors":"Shekhar Kedia, Emre Fertan, Yunzhao Wu, Yu P. Zhang, Georg Meisl, Jeff Y.L. Lam, Frances K. Wiseman, William A. McEwan, Annelies Quaegebeur, Maria Grazia Spillantini, John S.H. Danial, David Klenerman","doi":"10.1016/j.chembiol.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.chembiol.2025.01.001","url":null,"abstract":"Synaptic dysfunction is a primary hallmark of both Alzheimer’s and Parkinson’s disease, leading to cognitive and behavioral decline. While alpha-synuclein, beta-amyloid, and tau are involved in the physiological functioning of synapses, their pathological aggregation has been linked to synaptopathology. The methodology for studying the small-soluble protein aggregates formed by these proteins is limited. Here we describe SynPull, a method combining single-molecule pull-down, super-resolution microscopy, and advanced computational analyses to characterize the protein aggregates in human and mouse synaptosomes. We show that AT8-positive tau aggregates are the predominant aggregate type in synaptosomes from postmortem Alzheimer’s disease brain, although the aggregate size does not change in disease. Meanwhile, the relatively smaller amount of alpha-synuclein and beta-amyloid aggregates found in the synapses are larger than the extra-synaptic ones. Collectively, these results show the utility of SynPull to study pathological aggregates in neurodegeneration, elucidating the disease mechanisms causing synaptic dysfunction.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"28 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

New opportunities in mechanistic and functional microbiome studies 机制和功能微生物组研究的新机遇

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.012

Judith Behnsen, Kerwyn Casey Huang, Matthew T. Sorbara, Meng C. Wang, Jun Yu, Melody Y. Zeng

引用次数: 0

Meet the authors: Katerina Jones, Camila Bernardo de Brito, and Mariana Xavier Byndloss 认识一下作者：卡特琳娜·琼斯、卡米拉·贝尔纳多·德·布里托和玛丽安娜·泽维尔·拜德罗斯

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.009

Katerina Jones, Camila Bernardo de Brito, Mariana Xavier Byndloss

引用次数: 0

Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway. 人类 AKR1C3 与 GPR84 的激动剂结合，并参与扩展的多胺途径。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 Epub Date: 2024-08-19 DOI: 10.1016/j.chembiol.2024.07.011

Natavan Dudkina, Hyun Bong Park, Deguang Song, Abhishek Jain, Sajid A Khan, Richard A Flavell, Caroline H Johnson, Noah W Palm, Jason M Crawford

{"title":"Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway.","authors":"Natavan Dudkina, Hyun Bong Park, Deguang Song, Abhishek Jain, Sajid A Khan, Richard A Flavell, Caroline H Johnson, Noah W Palm, Jason M Crawford","doi":"10.1016/j.chembiol.2024.07.011","DOIUrl":"10.1016/j.chembiol.2024.07.011","url":null,"abstract":"Altered human aldo-keto reductase family 1 member C3 (AKR1C3) expression has been associated with poor prognosis in diverse cancers, ferroptosis resistance, and metabolic diseases. Despite its clinical significance, the endogenous biochemical roles of AKR1C3 remain incompletely defined. Using untargeted metabolomics, we identified a major transformation mediated by AKR1C3, in which a spermine oxidation product \"sperminal\" is reduced to \"sperminol.\" Sperminal causes DNA damage and activates the DNA double-strand break response, whereas sperminol induces autophagy in vitro. AKR1C3 also pulls down acyl-pyrones and pyrone-211 inhibits AKR1C3 activity. Through G protein-coupled receptor ligand screening, we determined that pyrone-211 is also a potent agonist of the semi-orphan receptor GPR84. Strikingly, mammalian fatty acid synthase produces acyl-pyrones in vitro, and this production is modulated by NADPH. Taken together, our studies support a regulatory role of AKR1C3 in an expanded polyamine pathway and a model linking fatty acid synthesis and NADPH levels to GPR84 signaling.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":" ","pages":"126-144.e18"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging biochemical, microbial and immunological evidence in the search for why HLA-B^∗27 confers risk for spondyloarthritis. 寻找 HLA-B∗27 为何会导致脊柱关节炎风险的生化、微生物和免疫学证据。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 Epub Date: 2024-08-20 DOI: 10.1016/j.chembiol.2024.07.012

Eric M Brown, Phuong N U Nguyen, Ramnik J Xavier

{"title":"Emerging biochemical, microbial and immunological evidence in the search for why HLA-B∗27 confers risk for spondyloarthritis.","authors":"Eric M Brown, Phuong N U Nguyen, Ramnik J Xavier","doi":"10.1016/j.chembiol.2024.07.012","DOIUrl":"10.1016/j.chembiol.2024.07.012","url":null,"abstract":"The strong association of the human leukocyte antigen B∗27 alleles (HLA-B∗27) with spondyloarthritis and related rheumatic conditions has long fascinated researchers, yet the precise mechanisms underlying its pathogenicity remain elusive. Here, we review how interplay between the microbiome, the immune system, and the enigmatic HLA-B∗27 could trigger spondyloarthritis, with a focus on whether HLA-B∗27 presents an arthritogenic peptide. We propose mechanisms by which the unique biochemical characteristics of the HLA-B∗27 protein structure, particularly its peptide binding groove, could dictate its propensity to induce pathological T cell responses. We further provide new insights into how TRBV9+ CD8+ T cells are implicated in the disease process, as well as how the immunometabolism of T cells modulates tissue-specific inflammatory responses in spondyloarthritis. Finally, we present testable models and suggest approaches to this problem in future studies given recent advances in computational biology, chemical biology, structural biology, and small-molecule therapeutics.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":" ","pages":"12-24"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens 代谢拔河：微生物代谢形成对肠道病原体的定植抗性

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.005

Katerina Jones, Camila Bernardo de Brito, Mariana Xavier Byndloss

引用次数: 0

Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome 评论衍生色氨酸代谢物强化皮肤屏障：来自人类皮肤微生物组的50种非生物模型的见解

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.007

Aayushi Uberoi, Sofía M. Murga-Garrido, Preeti Bhanap, Amy E. Campbell, Simon A.B. Knight, Monica Wei, Anya Chan, Taylor Senay, Saba Tegegne, Ellen K. White, Carrie Hayes Sutter, Clementina Mesaros, Thomas R. Sutter, Elizabeth A. Grice

{"title":"Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome","authors":"Aayushi Uberoi, Sofía M. Murga-Garrido, Preeti Bhanap, Amy E. Campbell, Simon A.B. Knight, Monica Wei, Anya Chan, Taylor Senay, Saba Tegegne, Ellen K. White, Carrie Hayes Sutter, Clementina Mesaros, Thomas R. Sutter, Elizabeth A. Grice","doi":"10.1016/j.chembiol.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.12.007","url":null,"abstract":"The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood. Tryptophan metabolites are AHR ligands that can be products of microbial metabolism. To identify microbially regulated tryptophan metabolites in vivo, we established a gnotobiotic model colonized with fifty human skin commensals and performed targeted mass spectrometry on murine skin. Indole-related metabolites were enriched in colonized skin compared to germ-free skin. In reconstructed human epidermis and in murine models of atopic-like barrier damage, these metabolites improved barrier repair and function individually and as a cocktail. These results provide a framework for the identification of microbial metabolites that mediate specific host functions, which can guide the development of microbe-based therapies for skin disorders.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"23 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Yeast paves the way for cancer immunotherapy 酵母为癌症免疫治疗铺平了道路

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.011

Dingjiacheng Jia, Shujie Chen

引用次数: 0

Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology. 肠道微生物群与表观遗传学之间的化学相互作用：对昼夜节律生物学的影响

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 Epub Date: 2024-05-21 DOI: 10.1016/j.chembiol.2024.04.016

Samskrathi Aravinda Sharma, Sarah Olanrewaju Oladejo, Zheng Kuang

{"title":"Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology.","authors":"Samskrathi Aravinda Sharma, Sarah Olanrewaju Oladejo, Zheng Kuang","doi":"10.1016/j.chembiol.2024.04.016","DOIUrl":"10.1016/j.chembiol.2024.04.016","url":null,"abstract":"Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":" ","pages":"61-82"},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Meet the authors: Aayushi Uberoi and Elizabeth A. Grice 来认识一下这篇文章的作者：银井青史和伊丽莎白·a·格赖斯

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2025-01-16 DOI: 10.1016/j.chembiol.2024.12.010

Aayushi Uberoi, Elizabeth A. Grice

引用次数: 0