Rikesh M Rajani, Robert Ellingford, Mariam Hellmuth, Samuel S Harris, Orjona S Taso, David Graykowski, Francesca Kar Wey Lam, Charles Arber, Emre Fertan, John S H Danial, Matthew Swire, Marcus Lloyd, Tatiana A Giovannucci, Mathieu Bourdenx, David Klenerman, Robert Vassar, Selina Wray, Carlo Sala Frigerio, Marc Aurel Busche
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引用次数: 0
Abstract
Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aβ in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aβ production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD.
减少淀粉样蛋白β（Aβ）已被证明能有效治疗阿尔茨海默病（AD），但神经元是致病性Aβ的主要来源这一基本假设尚未得到验证。在这里，我们通过证明少突胶质细胞是人脑中 Aβ 的重要来源，并在促进 AD 基因敲入小鼠模型中神经元异常亢进中发挥关键作用，对这一普遍看法提出了挑战。我们的研究表明，选择性抑制少突胶质细胞 Aβ 的产生可改善 AD 小鼠模型的大脑病理学，并恢复其体内神经元的功能。我们的研究结果表明，针对少突胶质细胞 Aβ 的产生可能是治疗 AD 的一种很有前景的治疗策略。
期刊介绍：
PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions.
The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public.
PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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