Cold Spring Harbor perspectives in medicine最新文献_第8页

The Complex Roles of Redox and Antioxidant Biology in Cancer. 氧化还原和抗氧化生物学在癌症中的复杂作用。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-01 DOI: 10.1101/cshperspect.a041546

Makiko Hayashi, Keito Okazaki, Thales Papgiannakopoulos, Hozumi Motohashi

{"title":"The Complex Roles of Redox and Antioxidant Biology in Cancer.","authors":"Makiko Hayashi, Keito Okazaki, Thales Papgiannakopoulos, Hozumi Motohashi","doi":"10.1101/cshperspect.a041546","DOIUrl":"10.1101/cshperspect.a041546","url":null,"abstract":"Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Restoration of Rod-Derived Metabolic and Redox Signaling to Prevent Blindness. 恢复杆衍生代谢和氧化还原信号以预防失明。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-01 DOI: 10.1101/cshperspect.a041284

Emmanuelle Clérin, Najate Aït-Ali, José-Alain Sahel, Thierry Léveillard

{"title":"Restoration of Rod-Derived Metabolic and Redox Signaling to Prevent Blindness.","authors":"Emmanuelle Clérin, Najate Aït-Ali, José-Alain Sahel, Thierry Léveillard","doi":"10.1101/cshperspect.a041284","DOIUrl":"10.1101/cshperspect.a041284","url":null,"abstract":"Vision is initiated by capturing photons in highly specialized sensory cilia known as the photoreceptor outer segment. Because of its lipid and protein composition, the outer segments are prone to photo-oxidation, requiring photoreceptors to have robust antioxidant defenses and high metabolic synthesis rates to regenerate the outer segments every 10 days. Both processes required high levels of glucose uptake and utilization. Retinitis pigmentosa is a prevalent form of inherited retinal degeneration characterized by initial loss of low-light vision caused by the death of rod photoreceptors. In this disease, rods die as a direct effect of an inherited mutation. Following the loss of rods, cones eventually degenerate, resulting in complete blindness. The progression of vision loss in retinitis pigmentosa suggested that rod photoreceptors were necessary to maintain healthy cones. We identified a protein secreted by rods that functions to promote cone survival, and we named it rod-derived cone viability factor (RdCVF). RdCVF is encoded by an alternative splice product of the nucleoredoxin-like 1 (NXNL1) gene, and RdCVF was found to accelerate the uptake of glucose by cones. Without RdCVF, cones eventually die because of compromised glucose uptake and utilization. The NXNL1 gene also encodes for the thioredoxin RdCVFL, which reduces cysteines in photoreceptor proteins that are oxidized, providing a defense against radical oxygen species. We will review here the main steps of discovering this novel intercellular signaling currently under translation as a broad-spectrum treatment for retinitis pigmentosa.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

α-Synuclein in Parkinson's Disease: 12 Years Later. 帕金森病中的α-突触核蛋白：12 年之后

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-01 DOI: 10.1101/cshperspect.a041645

Kostas Vekrellis, Evangelia Emmanouilidou, Maria Xilouri, Leonidas Stefanis

{"title":"α-Synuclein in Parkinson's Disease: 12 Years Later.","authors":"Kostas Vekrellis, Evangelia Emmanouilidou, Maria Xilouri, Leonidas Stefanis","doi":"10.1101/cshperspect.a041645","DOIUrl":"10.1101/cshperspect.a041645","url":null,"abstract":"α-Synuclein (AS) is a small presynaptic protein that is genetically, biochemically, and neuropathologically linked to Parkinson's disease (PD) and related synucleinopathies. We present here a review of the topic of this relationship, focusing on more recent knowledge. In particular, we review the genetic evidence linking AS to familial and sporadic PD, including a number of recently identified point mutations in the SNCA gene. We briefly go over the relevant neuropathological findings, stressing the evidence indicating a correlation between aberrant AS deposition and nervous system dysfunction. We analyze the structural characteristics of the protein, in relation to both its physiologic and pathological conformations, with particular emphasis on posttranslational modifications, aggregation properties, and secreted forms. We review the interrelationship of AS with various cellular compartments and functions, with particular focus on the synapse and protein degradation systems. We finally go over the recent exciting data indicating that AS can provide the basis for novel robust biomarkers in the field of synucleinopathies, while at the same time results from the first clinical trials specifically targeting AS are being reported.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Animal Models of Human Type 1 Diabetes. 推动人类 1 型糖尿病动物模型的发展。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-10-01 DOI: 10.1101/cshperspect.a041587

David V Serreze, Jennifer R Dwyer, Jeremy J Racine

引用次数: 0

Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals. 视网膜退化的啮齿类动物模型：从培养的纯化细胞到活体动物。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-10-01 DOI: 10.1101/cshperspect.a041311

Valérie Fradot, Sébastien Augustin, Valérie Fontaine, Katia Marazova, Xavier Guillonneau, José A Sahel, Serge Picaud

{"title":"Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals.","authors":"Valérie Fradot, Sébastien Augustin, Valérie Fontaine, Katia Marazova, Xavier Guillonneau, José A Sahel, Serge Picaud","doi":"10.1101/cshperspect.a041311","DOIUrl":"10.1101/cshperspect.a041311","url":null,"abstract":"Rodent models of retinal degeneration are essential for the development of therapeutic strategies. In addition to living animal models, we here also discuss models based on rodent cell cultures, such as purified retinal ganglion cells and retinal explants. These ex vivo models extend the possibilities for investigating pathological mechanisms and assessing the neuroprotective effect of pharmacological agents by eliminating questions on drug pharmacokinetics and bioavailability. The number of living rodent models has greatly increased with the possibilities to achieve transgenic modifications in animals for knocking in and out genes and mutations. The Cre-lox system has further enabled investigators to target specific genes or mutations in specific cells at specific stages. However, chemically or physically induced models can provide alternatives to such targeted gene modifications. The increased diversity of rodent models has widened our possibility to address most ocular pathologies for providing initial proof of concept of innovative therapeutic strategies.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding the Warburg Effect in Cancer. 了解癌症中的沃伯格效应

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041532

Zhaoqi Li, Muhammad Bin Munim, Daniel A Sharygin, Brooke J Bevis, Matthew G Vander Heiden

引用次数: 0

Imaging Approaches in Cancer Biology. 癌症生物学中的成像方法。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-03 DOI: 10.1101/cshperspect.a041349

Nirakar Rajbhandari, Emily Diaz, Marcie Kritzik, Tannishtha Reya

引用次数: 0

History of Finding Genes and Mutations Causing Inherited Retinal Diseases. 发现导致遗传性视网膜疾病的基因和突变的历史。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-03 DOI: 10.1101/cshperspect.a041287

Stephen P Daiger, Lori S Sullivan, Elizabeth L Cadena, Sara J Bowne

引用次数: 0

The Pathogenesis of Type 1 Diabetes 1 型糖尿病的发病机制

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041623

Kevan C. Herold, Jeffrey P. Krischer

{"title":"The Pathogenesis of Type 1 Diabetes","authors":"Kevan C. Herold, Jeffrey P. Krischer","doi":"10.1101/cshperspect.a041623","DOIUrl":"https://doi.org/10.1101/cshperspect.a041623","url":null,"abstract":"Type 1 diabetes (T1D) is a chronic autoimmune disease with a metabolic outcome. Studies over the past decades, have identified the contributions of genetics, environmental factors, and disorders of innate and adaptive immunity that collectively cause β-cell killing. The risk for T1D can be genetically identified but genotypes alone do not identify factors that lead to disease progression. The incidence of T1D has been increasing in the past few decades, which may be due to reduced exposure to infections and other environmental factors that can reduce autoimmunity (hygiene hypothesis). Once initiated, the disease pathogenesis progresses through stages that have been defined on the bases of immunologic (i.e., autoantibodies) and metabolic markers (glucose tolerance). The stages only loosely capture the risk for the time to diagnosis of disease, do not directly reflect disease activity, and there may be variance in the rate of progression within stages. In a general way, the stages can be used to identify patients at risk in whom interventions may be considered to modulate progression. This was achieved with the approval of teplizumab, a humanized anti-CD3 monoclonal antibody, for delaying the diagnosis of T1D.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"44 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Human Pancreas in Type 1 Diabetes: Lessons Learned from the Network of Pancreatic Organ Donors with Diabetes 1 型糖尿病患者的人体胰腺：从糖尿病胰腺器官捐赠者网络中汲取的经验教训

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041588

Irina Kusmartseva, Amanda Posgai, Mingder Yang, Richard Oram, Mark Atkinson, Alberto Pugliese, Carmella Evans-Molina

{"title":"The Human Pancreas in Type 1 Diabetes: Lessons Learned from the Network of Pancreatic Organ Donors with Diabetes","authors":"Irina Kusmartseva, Amanda Posgai, Mingder Yang, Richard Oram, Mark Atkinson, Alberto Pugliese, Carmella Evans-Molina","doi":"10.1101/cshperspect.a041588","DOIUrl":"https://doi.org/10.1101/cshperspect.a041588","url":null,"abstract":"The Network for Pancreatic Organ Donors with Diabetes (nPOD) has helped shape the contemporary understanding of type 1 diabetes (T1D) pathogenesis in humans through the procurement, distribution to scientists, and collaborative study of human pancreata and disease-related tissues from organ donors with T1D and islet autoantibody positivity. Since its inception in 2007, nPOD has collected tissues from 600 donors, and these resources have been distributed across 22 countries to more than 290 projects, resulting in nearly 350 publications. Research projects supported by nPOD span the breadth of diabetes research, including studies on T1D immunology and β-cell biology, and have uniquely unveiled abnormalities in other pancreatic cell types. In this article, we will detail the history and programmatic features of nPOD, as well as highlight key scientific findings from nPOD studies. We will present our view for the future of nPOD and discuss how the success of the program has established a precedent whereby knowledge gaps in biomedical research can be addressed through the study of human tissues.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"57 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0