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Relevance of transgenic mouse models for Alzheimer's disease
Progress in Molecular Biology and Translational Science Pub Date : 2020-08-24 , DOI: 10.1016/bs.pmbts.2020.07.007
Leon M Tai 1 , Juan Maldonado Weng 1 , Mary Jo LaDu 1 , Scott T Brady 1
Affiliation  

Over the last several decades, a number of mouse models have been generated for mechanistic and preclinical therapeutic research on Alzheimer's disease (AD)-like behavioral impairments and pathology. Acceptance or rejection of these models by the scientific community is playing a prominent role in how research findings are viewed and whether grants get funded and manuscripts published. The question of whether models are useful has become an exceptionally contentious issue. Much time and effort have gone into investigators debating comments such as “there are no mouse models of AD,” “…nice work but needs to be tested in another mouse model,” or “only data from humans is valid.” This leads to extensive written justifications for the choice of a model in grant applications, to the point of almost apologizing for the use of models. These debates also lead to initiatives to create new, better models of AD without consideration of what “better” may mean in this context. On the “other side,” an argument supporting the use of mouse models is one cannot dissect a biological mechanism in postmortem human tissue. In this chapter, we examine issues that we believe must be addressed if in vivo AD research is to progress. We opine that it is not the models that are the issue, but rather a lack of understanding the aspects of AD-like pathology the models were designed to mimic. The goal here is to improve the utilization of models to address critical issues, not to offer a critique of existing models or make endorsements.



中文翻译:

阿尔茨海默病转基因小鼠模型的相关性

在过去的几十年里,已经产生了许多小鼠模型,用于阿尔茨海默病 (AD) 样行为障碍和病理的机械和临床前治疗研究。科学界对这些模型的接受或拒绝在如何看待研究结果以及是否获得资助和手稿出版方面发挥着重要作用。模型是否有用的问题已成为一个极具争议的问题。研究人员花费了大量时间和精力来辩论诸如“没有 AD 小鼠模型”、“……不错的工作,但需要在另一个小鼠模型中进行测试”或“只有来自人类的数据有效”等评论。这导致了在资助申请中选择模型的大量书面理由,以至于几乎为模型的使用道歉。这些辩论还导致了创建新的、更好的 AD 模型的举措,而不考虑在这种情况下“更好”可能意味着什么。另一方面,支持使用小鼠模型的论点是无法剖析死后人体组织中的生物学机制。在本章中,我们研究了我们认为如果体内 AD 研究要取得进展必须解决的问题。我们认为,问题不在于模型,而在于缺乏对模型旨在模仿的 AD 样病理学方面的理解。这里的目标是提高模型的利用率以解决关键问题,而不是对现有模型进行批评或认可。”支持使用小鼠模型的论点是无法剖析死后人体组织中的生物机制。在本章中,我们研究了我们认为如果体内 AD 研究要取得进展必须解决的问题。我们认为,问题不在于模型,而在于缺乏对模型旨在模仿的 AD 样病理学方面的理解。这里的目标是提高模型的利用率以解决关键问题,而不是对现有模型进行批评或认可。”支持使用小鼠模型的论点是无法剖析死后人体组织中的生物机制。在本章中,我们研究了我们认为如果体内 AD 研究要取得进展必须解决的问题。我们认为,问题不在于模型,而在于缺乏对模型旨在模仿的 AD 样病理学方面的理解。这里的目标是提高模型的利用率以解决关键问题,而不是对现有模型进行批评或认可。而是缺乏对模型旨在模仿的 AD 样病理学方面的了解。这里的目标是提高模型的利用率以解决关键问题,而不是对现有模型进行批评或认可。而是缺乏对模型旨在模仿的 AD 样病理学方面的了解。这里的目标是提高模型的利用率以解决关键问题,而不是对现有模型进行批评或认可。

更新日期:2020-08-24
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