Life medicine最新文献_第10页

Manipulating Autophagic Degradation in Human Diseases: from Mechanisms to Interventions 操纵人类疾病中的自噬降解：从机制到干预

Life medicine Pub Date : 2022-10-11 DOI: 10.1093/lifemedi/lnac043

Yiqing Zhang, Xiaoxia Liu, D. Klionsky, B. Lu, Q. Zhong

{"title":"Manipulating Autophagic Degradation in Human Diseases: from Mechanisms to Interventions","authors":"Yiqing Zhang, Xiaoxia Liu, D. Klionsky, B. Lu, Q. Zhong","doi":"10.1093/lifemedi/lnac043","DOIUrl":"https://doi.org/10.1093/lifemedi/lnac043","url":null,"abstract":"\u0000 Targeted degradation, having emerged as a powerful and promising strategy in drug discovery in the past two decades, has provided a solution for many once undruggable targets involved in various diseases. While earlier targeted degradation tools, as exemplified by PROteolysis-TArgeting Chimera (PROTAC), focused on harnessing the ubiquitin-proteasome system, novel approaches that aim to utilize autophagy, a potent, lysosome-dependent degradation pathway, have also surfaced recently as promising modalities. In this Review, we first introduce the mechanisms that establish selectivity in autophagy, which provides the rationales for autophagy-based targeted degradation; we also provide an overview on the panoply of cellular machinery involved in this process, an arsenal that could be potentially harnessed. On this basis, we propose four strategies for designing autophagy-based targeted degraders, including Tagging Targets, Directly Engaging Targets, Initiating Autophagy at Targets, and Phagophore-Tethering to Targets. We introduce the current frontiers in this field, including AUtophagy-TArgeting Chimera (AUTAC), Targeted Protein Autophagy (TPA), AUTOphagy-TArgeting Chimera (AUTOTAC, not to be confused with AUTAC), AuTophagosome TEthering Compound (ATTEC), and other experimental approaches as case studies for each strategy. Finally, we put forward a workflow for generating autophagy-based degraders and some important questions that may guide and inspire the process.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44905345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Continuous antioxidant drug exposure: a bridge from ideal world to real world of therapy for amyotrophic lateral sclerosis 持续抗氧化药物暴露：肌萎缩侧索硬化症治疗从理想世界到现实世界的桥梁

Life medicine Pub Date : 2022-10-08 DOI: 10.1093/lifemedi/lnac042

Jun Wang, Xin-Fu Zhou, Yanjiang Wang

引用次数: 2

Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging. 以衰老细胞为目标实现更健康的长寿:全球老龄化时代的路线图。

Life medicine Pub Date : 2022-10-01 DOI: 10.1093/lifemedi/lnac030

Yu Sun, Qingfeng Li, James L Kirkland

{"title":"Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging.","authors":"Yu Sun, Qingfeng Li, James L Kirkland","doi":"10.1093/lifemedi/lnac030","DOIUrl":"https://doi.org/10.1093/lifemedi/lnac030","url":null,"abstract":"<p><p>Aging is a natural but relentless process of physiological decline, leading to physical frailty, reduced ability to respond to physical stresses (resilience) and, ultimately, organismal death. Cellular senescence, a self-defensive mechanism activated in response to intrinsic stimuli and/or exogenous stress, is one of the central hallmarks of aging. Senescent cells cease to proliferate, while remaining metabolically active and secreting numerous extracellular factors, a feature known as the senescence-associated secretory phenotype. Senescence is physiologically important for embryonic development, tissue repair, and wound healing, and prevents carcinogenesis. However, chronic accumulation of persisting senescent cells contributes to a host of pathologies including age-related morbidities. By paracrine and endocrine mechanisms, senescent cells can induce inflammation locally and systemically, thereby causing tissue dysfunction, and organ degeneration. Agents including those targeting damaging components of the senescence-associated secretory phenotype or inducing apoptosis of senescent cells exhibit remarkable benefits in both preclinical models and early clinical trials for geriatric conditions. Here we summarize features of senescent cells and outline strategies holding the potential to be developed as clinical interventions. In the long run, there is an increasing demand for safe, effective, and clinically translatable senotherapeutics to address healthcare needs in current settings of global aging.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"1 2","pages":"103-119"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9191171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Decoding liver fibrogenesis with single-cell technologies 用单细胞技术解码肝纤维化

Life medicine Pub Date : 2022-09-29 DOI: 10.1093/lifemedi/lnac040

Tingting Zhou, M. Kiran, K. O. Lui, Q. Ding

{"title":"Decoding liver fibrogenesis with single-cell technologies","authors":"Tingting Zhou, M. Kiran, K. O. Lui, Q. Ding","doi":"10.1093/lifemedi/lnac040","DOIUrl":"https://doi.org/10.1093/lifemedi/lnac040","url":null,"abstract":"\u0000 Liver fibrogenesis is a highly dynamic and complex process that drives the progression of chronic liver disease towards liver failure and end-stage liver diseases. Despite decades of intense studies, the cellular and molecular mechanisms underlying liver fibrogenesis remain elusive, and no approved therapies to treat liver fibrosis are currently available. The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows the characterization of cellular alterations under healthy and diseased conditions at an unprecedented resolution. In this Review, we discuss how the scRNA-seq studies are transforming our understanding of the regulatory mechanisms of liver fibrosis. We specifically emphasize discoveries on disease-relevant cell subpopulations, molecular events, and cell interactions on cell types including hepatocytes, liver sinusoidal endothelial cells, myofibroblasts and macrophages. These discoveries have uncovered critical pathophysiological changes during liver fibrogenesis. Further efforts are urged to fully understand the functional contributions of these changes to liver fibrogenesis, and to translate the new knowledge into effective therapeutic approaches.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44840855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Retrotransposon: A Versatile Player in Human Preimplantation Development and Health 逆转录转座子：人类植入前发育和健康的全能参与者

Life medicine Pub Date : 2022-09-25 DOI: 10.1093/lifemedi/lnac041

Yuliang Qu, Z. Izsvák, Jichang Wang

引用次数: 3

YAP/TAZ links mechanosensing to aging YAP/TAZ将机械传感与老化联系起来

Life medicine Pub Date : 2022-09-12 DOI: 10.1093/lifemedi/lnac039

Xiaolei Cao, Wenqi Wang, Bin Zhao

引用次数: 2

Elucidating the developmental dynamics of mouse stromal cells at single-cell level 在单细胞水平上阐明小鼠间质细胞的发育动力学

Life medicine Pub Date : 2022-09-05 DOI: 10.1093/lifemedi/lnac037

Xing Fang, Mengmeng Jiang, Mingyong Zhou, Jikai Shao, Xiunan Fang, Jingjing Wang, Yuting Fu, Yuan Liao, Haide Chen, Renying Wang, Lijiang Fei, Huiyu Sun, Peijing Zhang, Jingang Huang, Xiaoping Han, Guoji Guo

引用次数: 1

Epileptic Networks Neurosurgery: Connectomes and hubs 癫痫网络神经外科：连接体和中枢

Life medicine Pub Date : 2022-08-30 DOI: 10.1093/lifemedi/lnac033

Kailiang Wang, P. Wei, Y. Shan, Guoguang Zhao

引用次数: 1

The Yin-Yang Functions of Macrophages in Metabolic Disorders 巨噬细胞在代谢紊乱中的阴阳功能

Life medicine Pub Date : 2022-08-30 DOI: 10.1093/lifemedi/lnac035

Juli Bai, Feng Liu

引用次数: 0

NTLA-2001: opening a new era for gene therapy NTLA-2001:开启基因治疗的新时代

Life medicine Pub Date : 2022-08-30 DOI: 10.1093/lifemedi/lnac036

T. Cui, Bojin Li, Wei Li

引用次数: 3