Cell Chemical Biology最新文献_第2页

Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications 精准表观遗传编辑：技术进步、持久挑战和治疗应用

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.007

{"title":"Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications","authors":"","doi":"10.1016/j.chembiol.2024.07.007","DOIUrl":"10.1016/j.chembiol.2024.07.007","url":null,"abstract":"<div><p>The epigenome is a complex framework through which gene expression is precisely and flexibly modulated to incorporate heritable memory and responses to environmental stimuli. It governs diverse cellular processes, including cell fate, disease, and aging. The need to understand this system and precisely control gene expression outputs for therapeutic purposes has precipitated the development of a diverse set of epigenetic editing tools. Here, we review the existing toolbox for targeted epigenetic editing, technical considerations of the current technologies, and opportunities for future development. We describe applications of therapeutic epigenetic editing and their potential for treating disease, with a discussion of ongoing delivery challenges that impede certain clinical interventions, particularly in the brain. With simultaneous advancements in available engineering tools and appropriate delivery technologies, we predict that epigenetic editing will increasingly cement itself as a powerful approach for safely treating a wide range of disorders in all tissues of the body.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400309X/pdfft?md5=d1b75cb9f1e6f7156ed373d1c1fdaec2&pid=1-s2.0-S245194562400309X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918647","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

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria 鉴定治疗疟疾的强效可逆哌啶羧酰胺类物种选择性口服活性蛋白酶体抑制剂

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.001

{"title":"Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria","authors":"","doi":"10.1016/j.chembiol.2024.07.001","DOIUrl":"10.1016/j.chembiol.2024.07.001","url":null,"abstract":"<div><p>Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant <em>Plasmodium falciparum</em> (<em>Pf</em>) parasites revealed point mutations in the <em>Pf_</em>proteasome β5 active-site (<em>Pf</em>β5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >10<sup>9</sup>) and was synergistic with dihydroartemisinin. <em>Pf_</em>proteasome purification was facilitated by His<sub>8</sub>-tag introduction onto β7. Inhibition of <em>Pf</em>β5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The <em>Pf_</em>proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the β5/β6/β3 subunit interface that has species differences between <em>Pf</em> and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624002782/pdfft?md5=d0d63c5b95768cd07bd4ad29366f279e&pid=1-s2.0-S2451945624002782-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141795066","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

A versatile residue numbering scheme for Nav and Cav channels Nav 和 Cav 信道的通用残差编号方案

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.008

引用次数: 0

The art of designed coiled-coils for the regulation of mammalian cells 设计用于调节哺乳动物细胞的盘绕线圈的艺术。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.06.001

引用次数: 0

Reflections from Nobel laureates in chemistry 诺贝尔化学奖获得者的思考

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.016

引用次数: 0

Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture 赛普特蛋白通过调控气敏D的裂解和ninjurin-1介导的质膜破裂促进巨噬细胞的脓毒症

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.003

{"title":"Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture","authors":"","doi":"10.1016/j.chembiol.2024.07.003","DOIUrl":"10.1016/j.chembiol.2024.07.003","url":null,"abstract":"<div><p>The septin cytoskeleton is primarily known for roles in cell division and host defense against bacterial infection. Despite recent insights, the full breadth of roles for septins in host defense is poorly understood. In macrophages, <em>Shigella</em> induces pyroptosis, a pro-inflammatory form of cell death dependent upon gasdermin D (GSDMD) pores at the plasma membrane and cell surface protein ninjurin-1 (NINJ1) for membrane rupture. Here, we discover that septins promote macrophage pyroptosis induced by lipopolysaccharide (LPS)/nigericin and <em>Shigella</em> infection, but do not affect cytokine expression or release. We observe that septin filaments assemble at the plasma membrane, and cleavage of GSDMD is impaired in septin-depleted cells. We found that septins regulate mitochondrial dynamics and the expression of NINJ1. Using a <em>Shigella</em>-zebrafish infection model, we show that septin-mediated pyroptosis is an <em>in vivo</em> mechanism of infection control. The discovery of septins as a mediator of pyroptosis may inspire innovative anti-bacterial and anti-inflammatory treatments.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003052/pdfft?md5=1fda9bdffaba472fc447836cdbe316e3&pid=1-s2.0-S2451945624003052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892170","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

AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells AspSnFR：用于实时监测活细胞中天冬氨酸的基因编码生物传感器

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.05.002

{"title":"AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells","authors":"","doi":"10.1016/j.chembiol.2024.05.002","DOIUrl":"10.1016/j.chembiol.2024.05.002","url":null,"abstract":"<div><p>Aspartate is crucial for nucleotide synthesis, ammonia detoxification, and maintaining redox balance via the malate-aspartate-shuttle (MAS). To disentangle these multiple roles of aspartate metabolism, tools are required that measure aspartate concentrations in real time and in live cells. We introduce AspSnFR, a genetically encoded green fluorescent biosensor for intracellular aspartate, engineered through displaying and screening biosensor libraries on mammalian cells. In live cells, AspSnFR is able to precisely and quantitatively measure cytosolic aspartate concentrations and dissect its production from glutamine. Combining high-content imaging of AspSnFR with pharmacological perturbations exposes differences in metabolic vulnerabilities of aspartate levels based on nutrient availability. Further, AspSnFR facilitates tracking of aspartate export from mitochondria through SLC25A12, the MAS’ key transporter. We show that SLC25A12 is a rapidly responding and direct route to couple Ca<sup>2+</sup> signaling with mitochondrial aspartate export. This establishes SLC25A12 as a crucial link between cellular signaling, mitochondrial respiration, and metabolism.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400179X/pdfft?md5=3b3153c35af18753feadccb80f236687&pid=1-s2.0-S245194562400179X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156564","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

Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies 调控诱导接近靶向嵌合体--RIPTACs--用于癌症选择性疗法的异功能小分子策略

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.005

引用次数: 0

The chemistry of electrical signaling in sodium channels from bacteria and beyond 细菌等钠离子通道中的电信号化学反应

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.010

{"title":"The chemistry of electrical signaling in sodium channels from bacteria and beyond","authors":"","doi":"10.1016/j.chembiol.2024.07.010","DOIUrl":"10.1016/j.chembiol.2024.07.010","url":null,"abstract":"<div><p>Electrical signaling is essential for all fast processes in biology, but its molecular mechanisms have been uncertain. This review article focuses on studies of bacterial sodium channels in order to home in on the essential molecular and chemical mechanisms underlying transmembrane ion conductance and voltage-dependent gating without the overlay of complex protein interactions and regulatory mechanisms in mammalian sodium channels. This minimalist approach has yielded a nearly complete picture of sodium channel function at the atomic level that are mostly conserved in mammalian sodium channels, including sodium selectivity and conductance, voltage sensing and activation, electromechanical coupling to pore opening and closing, slow inactivation, and pathogenic dysfunction in a debilitating channelopathy. Future studies of nature’s simplest sodium channels may continue to yield key insights into the fundamental molecular and chemical principles of their function and further elucidate the chemical basis of electrical signaling.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400312X/pdfft?md5=0c34706ac158a70d52d3dd2d116ee049&pid=1-s2.0-S245194562400312X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990568","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: Xueqin Jin, Jian Huang, Huan Wang, Kan Wang, and Nieng Yan 与作者见面金雪琴、黄健、王欢、王侃和严能

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-08-15 DOI: 10.1016/j.chembiol.2024.07.009

引用次数: 0