دورية أكاديمية
N,N-dimethylacetamide targets neuroinflammation in Alzheimer’s disease in in-vitro and ex-vivo models
| العنوان: | N,N-dimethylacetamide targets neuroinflammation in Alzheimer’s disease in in-vitro and ex-vivo models |
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| المؤلفون: | Zeng-Hui Wei, Jagadish Koya, Nikita Acharekar, Jesus Trejos, Xing-Duo Dong, Francis A. Schanne, Charles R. Ashby, Sandra E. Reznik |
| المصدر: | Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023) |
| بيانات النشر: | Nature Portfolio, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Alzheimer’s disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60–80% of cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo models of AD. We show that DMA significantly suppresses the production of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO) and various cytokines and chemokines, as well as amyloid-β (Aβ), in cultured microglia and organotypic hippocampal slices induced by lipopolysaccharide (LPS). We also demonstrate that DMA inhibits Aβ-induced inflammation. Finally, we show that the mechanism of DMA’s effect on neuroinflammation is inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway and we show how DMA dismantles the positive feedback loop between NF-κB and Aβ synthesis. Taken together, our findings suggest that DMA, a generally regarded as safe compound that crosses the blood brain barrier, should be further investigated as a potential therapy for Alzheimer’s disease and neuroinflammatory disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-34355-w |
| URL الوصول: | https://doaj.org/article/893fcb60e9304622ad9b4df38e80801f |
| رقم الأكسشن: | edsdoj.893fcb60e9304622ad9b4df38e80801f |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-34355-w |