Nature Reviews Molecular Cell Biology最新文献_第5页

Structural biology and molecular pharmacology of voltage-gated ion channels 电压门控离子通道的结构生物学和分子药理学。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-05 DOI: 10.1038/s41580-024-00763-7

Jian Huang, Xiaojing Pan, Nieng Yan

{"title":"Structural biology and molecular pharmacology of voltage-gated ion channels","authors":"Jian Huang, Xiaojing Pan, Nieng Yan","doi":"10.1038/s41580-024-00763-7","DOIUrl":"10.1038/s41580-024-00763-7","url":null,"abstract":"Voltage-gated ion channels (VGICs), including those for Na+, Ca2+ and K+, selectively permeate ions across the cell membrane in response to changes in membrane potential, thus participating in physiological processes involving electrical signalling, such as neurotransmission, muscle contraction and hormone secretion. Aberrant function or dysregulation of VGICs is associated with a diversity of neurological, psychiatric, cardiovascular and muscular disorders, and approximately 10% of FDA-approved drugs directly target VGICs. Understanding the structure–function relationship of VGICs is crucial for our comprehension of their working mechanisms and role in diseases. In this Review, we discuss how advances in single-particle cryo-electron microscopy have afforded unprecedented structural insights into VGICs, especially on their interactions with clinical and investigational drugs. We present a comprehensive overview of the recent advances in the structural biology of VGICs, with a focus on how prototypical drugs and toxins modulate VGIC activities. We explore how these structures elucidate the molecular basis for drug actions, reveal novel pharmacological sites, and provide critical clues to future drug discovery. Voltage-gated ion channels (VGICs) regulate ion permeability in multiple physiological processes, thereby representing important disease targets. This Review discusses how advances in cryo-electron microscopy have contributed to our understanding of VGIC structures and mechanisms and their interactions with drugs.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"904-925"},"PeriodicalIF":81.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893875","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

MYB-related proteins make chloroplasts 与 MYB 相关的蛋白质使叶绿体

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-08-02 DOI: 10.1038/s41580-024-00771-7

Kim Baumann

引用次数: 0

What does it take to build a nucleus? 构建原子核需要什么？

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-24 DOI: 10.1038/s41580-024-00766-4

Abigail Buchwalter

引用次数: 0

Regulation of and challenges in targeting NAD+ metabolism 针对 NAD+ 代谢的调节和挑战。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-18 DOI: 10.1038/s41580-024-00752-w

Marie E. Migaud, Mathias Ziegler, Joseph A. Baur

{"title":"Regulation of and challenges in targeting NAD+ metabolism","authors":"Marie E. Migaud, Mathias Ziegler, Joseph A. Baur","doi":"10.1038/s41580-024-00752-w","DOIUrl":"10.1038/s41580-024-00752-w","url":null,"abstract":"Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction–oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+ levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+ levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+ and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+ metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+ supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+ and NADH, and non-canonical NAD+ and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+ levels in humans. Nicotinamide adenine dinucleotide (NAD+) has essential roles in metabolism and can be readily supplemented, potentially to benefit human health. This Review discusses recent insights into the roles of the microbiome and cellular compartments in regulating NAD+ metabolism, and the promise and pitfalls of NAD+ supplementation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"822-840"},"PeriodicalIF":81.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723970","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

Cellular and pathological functions of tau tau 的细胞和病理功能

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-16 DOI: 10.1038/s41580-024-00753-9

Celeste Parra Bravo, Sarah A. Naguib, Li Gan

{"title":"Cellular and pathological functions of tau","authors":"Celeste Parra Bravo, Sarah A. Naguib, Li Gan","doi":"10.1038/s41580-024-00753-9","DOIUrl":"10.1038/s41580-024-00753-9","url":null,"abstract":"Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions. Tau is a microtubule-binding protein that is expressed primarily in neurons. The abnormal accumulation of tau aggregates in neurons is associated with neurodegenerative diseases, known as tauopathies, such as Alzheimer disease and frontotemporal dementia. This Review discusses recent insights into the diverse cellular functions of tau, the pathology of tau aggregates and the potential for therapeutic interventions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"845-864"},"PeriodicalIF":81.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625090","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

The discovery of cyclin-dependent kinases 依赖细胞周期蛋白的激酶的发现

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-15 DOI: 10.1038/s41580-024-00765-5

Paul Nurse

引用次数: 0

Virus–host warfare by PROTACs PROTAC 的病毒-宿主战争

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-09 DOI: 10.1038/s41580-024-00761-9

Kylie J. Walters

引用次数: 0

Long-lived proteomes in healthy ovaries 健康卵巢中的长寿命蛋白质组

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-05 DOI: 10.1038/s41580-024-00764-6

Eytan Zlotorynski

引用次数: 0

Heterochromatin as a balancing act between transcription and gene silencing 异染色质是转录和基因沉默之间的平衡。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-03 DOI: 10.1038/s41580-024-00762-8

Sigurd Braun

引用次数: 0

Resolution in super-resolution microscopy — definition, trade-offs and perspectives 超分辨率显微镜的分辨率--定义、权衡与展望。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1038/s41580-024-00755-7

Kirti Prakash, David Baddeley, Christian Eggeling, Reto Fiolka, Rainer Heintzmann, Suliana Manley, Aleksandra Radenovic, Carlas Smith, Hari Shroff, Lothar Schermelleh

引用次数: 0