Cold Spring Harbor perspectives in medicine最新文献

Dopamine Cell-Based Replacement Therapies. 基于多巴胺细胞的替代疗法。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-05 DOI: 10.1101/cshperspect.a041611

Saeed Kayhanian, Roger A Barker

{"title":"Dopamine Cell-Based Replacement Therapies.","authors":"Saeed Kayhanian, Roger A Barker","doi":"10.1101/cshperspect.a041611","DOIUrl":"https://doi.org/10.1101/cshperspect.a041611","url":null,"abstract":"Parkinson's disease (PD) is a common disorder that has, as part of its core pathology, the loss of the nigral dopaminergic nerve cells that project to the striatum. Replacing this loss with dopaminergic drugs has been the mainstay of therapy in PD for more than 50 years and while offering significant clinical benefit, especially in early-stage disease, leads to side effects over time. A conceptually more effective way to treat this aspect of the PD pathology would be to replace the missing dopaminergic system with grafts of new dopamine cells. This approach has been investigated for nearly 40 years using a variety of different dopamine cell sources. To date, a proof-of-principle has been shown using human fetal dopamine cells in patients with PD, but the more widespread adoption of this approach has been hampered by logistical reasons around tissue supply, the ethics of the cell source, and, most importantly, by the inconsistent results shown across trials, which in some cases have reported worrying side effects. Reasons for all this have been discussed extensively in the literature and one solution may lie in the development of new human stem cell-derived dopamine cells, which are now just entering first in human clinical trials.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582429","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

Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities. 癌症代谢：历史里程碑、新概念和新机遇》（Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities）。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-05 DOI: 10.1101/cshperspect.a041814

Navdeep S Chandel, Karen H Vousden, Ralph J DeBerardinis

引用次数: 0

Epitope Hierarchy in Type 1 Diabetes Pathogenesis. 1 型糖尿病发病机制中的表位层次。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-11-05 DOI: 10.1101/cshperspect.a041594

Thomas Delong, Maki Nakayama

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":null,"pages":null},"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

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":null,"pages":null},"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

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":null,"pages":null},"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":null,"pages":null},"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

Ovarian Clear Cell Carcinoma: An Endometriosis-Associated Cancer with Therapeutic Challenges. 卵巢透明细胞癌：子宫内膜异位症相关癌症的治疗难题。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041315

Ruby Yun-Ju Huang, Jimmy Jin-Che Lin

引用次数: 0