Drug Discovery Today: Disease Models最新文献_第6页

What have we learned so far on the molecular pathogenesis of Werner syndrome using mutant mouse models of this human progeroid disorder? 到目前为止，我们对使用人类早老性疾病的突变小鼠模型的Werner综合征的分子发病机制有什么了解

Drug Discovery Today: Disease Models Pub Date : 2018-03-01 DOI: 10.1016/j.ddmod.2018.12.002

Michel Lebel , F. Brad Johnson

{"title":"What have we learned so far on the molecular pathogenesis of Werner syndrome using mutant mouse models of this human progeroid disorder?","authors":"Michel Lebel , F. Brad Johnson","doi":"10.1016/j.ddmod.2018.12.002","DOIUrl":"10.1016/j.ddmod.2018.12.002","url":null,"abstract":"<div>Werner syndrome (WS) is a rare autosomal recessive disorder characterized by genomic instability and the premature onset of several age-associated phenotypes. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication, repair, telomere maintenance, and transcription. This review focuses on experimental mouse models that have been generated to understand the molecular impact of different mutations in the Wrn orthologue on oxidative stress, inflammation, telomere maintenance, and transcription in different tissues. Appropriate crosses between Wrn mutant mice and transgenic or knockout models of genes important in cell cycle or DNA repair genes have highlighted the importance of the WRN protein in biological processes regulating cell proliferation, senescence, and apoptosis. Finally, this short review recognizes the limitations and translational values of such mouse models.</div>","PeriodicalId":39774,"journal":{"name":"Drug Discovery Today: Disease Models","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmod.2018.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88171470","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: 0

A primer on ageing studies in mice: Considerations, opportunities and limitations 小鼠衰老研究的入门:考虑、机会和限制

Drug Discovery Today: Disease Models Pub Date : 2018-03-01 DOI: 10.1016/j.ddmod.2019.01.002

Paul K. Potter

引用次数: 0

Mouse models of central nervous system ageing 小鼠中枢神经系统衰老模型

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.10.002

Yang Heng, Bart J.L. Eggen, Erik W.G.M. Boddeke, Susanne M. Kooistra

引用次数: 6

Refinement of the MPTP model for Parkinson’s disease in the marmoset 狨猴帕金森病MPTP模型的改进

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.10.003

Ingrid H.C.H.M Philippens

{"title":"Refinement of the MPTP model for Parkinson’s disease in the marmoset","authors":"Ingrid H.C.H.M Philippens","doi":"10.1016/j.ddmod.2018.10.003","DOIUrl":"10.1016/j.ddmod.2018.10.003","url":null,"abstract":"<div>The increasing prevalence of age-related neurodegenerative diseases is a growing concern for the ageing societies. Parkinson’s disease is a major progressive motor disorder of the brain caused by specific degeneration of the dopamine-producing neurons in the substantia nigra, which govern the control of muscle movement. Despite intensive research efforts, no cure has been found, and we still have to rely on symptom control treatment. The paucity of valid preclinical models that faithfully reproduce clinical and pathogenic features of neurodegenerative diseases is a main cause of the lack of effective treatments. The MPTP-treated common marmoset monkey can bridge this gap by providing an appropriate animal model for construct, face and predictive validity. The neurotoxin MPTP causes selective cell death in the dopamine neurons. However, there is still a debate about the level of discomfort in the MPTP primate model. Refinement of the MPTP marmoset model-by lowering the dosage and increasing the interval-prevents the interference of direct effects of the toxin MPTP on clinical signs that might have an impact on the outcome of the result. This will also improve the discomfort for the animal as the progression of the clinical features develop slowly over time, which also mimicking the human counterpart of PD. Finetuning of the MPTP-induction protocol may, therefore, improve the wellbeing of the animal and development of rational, effective treatments for the multi-factorial pathogenic mechanisms of PD.</div>","PeriodicalId":39774,"journal":{"name":"Drug Discovery Today: Disease Models","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmod.2018.10.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82094734","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: 1

The ME7 prion model of neurodegeneration as a tool to understand and target neuroinflammation in Alzheimer’s disease 神经退行性变的ME7朊病毒模型作为了解和靶向阿尔茨海默病神经炎症的工具

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.10.004

Joe K. Chouhan , Susan B. Fowler , Carl I. Webster , Jessica L. Teeling

引用次数: 4

Modelling amyotrophic lateral sclerosis in mice 小鼠肌萎缩侧索硬化模型

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.10.001

Jodie Stephenson , Sandra Amor

引用次数: 13

Cuprizone as a model of myelin and axonal damage 铜酮作为髓鞘和轴突损伤的模型

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.09.003

Stella Nyamoya , Felix Schweiger , Markus Kipp , Tanja Hochstrasser

引用次数: 6

Models of neuroimmune and neurodegenerative diseases 神经免疫和神经退行性疾病模型

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.11.002

Sandra Amor

引用次数: 1

Neural cell cultures to study spinal cord injury 神经细胞培养研究脊髓损伤

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.10.005

George A. McCanney, Michael J. Whitehead, Michael A. McGrath, Susan L. Lindsay, Susan C. Barnett

{"title":"Neural cell cultures to study spinal cord injury","authors":"George A. McCanney, Michael J. Whitehead, Michael A. McGrath, Susan L. Lindsay, Susan C. Barnett","doi":"10.1016/j.ddmod.2018.10.005","DOIUrl":"10.1016/j.ddmod.2018.10.005","url":null,"abstract":"<div>There are great challenges involved in identifying potential therapies for the repair of spinal cord injury (SCI). It is well accepted that not one, but a combination of therapeutic strategies will be required to effectively repair the damage. However, identifying novel therapeutics is hindered by the lack of reliable methods available that facilitate high throughput screening of numerous compounds. While the use of animals provides an important means for testing new therapies, in vivo models of SCI can be time consuming and require the use of large cohorts of animals. In this review, we have focused on three aspects of repair following SCI (1) neurite outgrowth, (2) glial scar and (3) remyelination. No in vitro model encapsulates all the features of SCI and we discuss the limitations and virtues of the various cultures, which range from individual cell-types through to complex co-cultures. We discuss how these cultures can be used as a moderate throughput screen to identify novel therapeutics for CNS repair before being verified in animal models.</div>","PeriodicalId":39774,"journal":{"name":"Drug Discovery Today: Disease Models","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmod.2018.10.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82307487","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: 4

Modelling in miniature: Using Drosophila melanogaster to study human neurodegeneration 微缩模型:用黑腹果蝇研究人类神经退行性变

Drug Discovery Today: Disease Models Pub Date : 2017-12-01 DOI: 10.1016/j.ddmod.2018.09.004

Roald Lambrechts , Anita Faber , Ody Sibon

{"title":"Modelling in miniature: Using Drosophila melanogaster to study human neurodegeneration","authors":"Roald Lambrechts , Anita Faber , Ody Sibon","doi":"10.1016/j.ddmod.2018.09.004","DOIUrl":"10.1016/j.ddmod.2018.09.004","url":null,"abstract":"<div>Despite great advances in clinical diagnostics, genetics and molecular biology, neurodegenerative diseases like Parkinson’s disease (PD), Alzheimer’s disease (AD) and Huntington’s disease (HD) still pose great challenges, both in terms of understanding their pathophysiology as well as their treatment. Organisms able to adequately model the intricacies of the disease mechanism and respose to potential treatment, whilst not compromising on ease of handling, studying and manipulating in order to study them, represent the holy grail of translational biology and medicine. Here, we review the suitability of the fruit fly, Drosophila melanogaster, as a model organism in the field of neurodegeneration. We briefly summarize the history of scientific research concerning this organism, review the molecular, genetic and pharmacological toolbox available and we discuss the ways this toolbox has been applied to research in neurodegeneration. Finally, by reviewing some findings in the fruit fly which were subsequently translated to and validated in other organisms on their way to the clinic, the power and robustness of Drosophila melanogaster is highlighted.</div>","PeriodicalId":39774,"journal":{"name":"Drug Discovery Today: Disease Models","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmod.2018.09.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88838815","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