CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease
| العنوان: | CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease |
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| المؤلفون: | Michael Bacher, Rakez Kayed, Anne Marie Hoppmann, Charles G. Glabe, Lars Lewejohann, Susanne Schnell, Philippe Marambaud, Nicole Goertz, Bayan Aljabari, Jens Klotsche, Yousef Al-Abed, Norbert Sachser, Kathy Keyvani, Richard Dodel |
| المصدر: | The Journal of Experimental Medicine Journal of Experimental Medicine, 2008, Bd. 205, Nr. 7, S. 1593-1599, ISSN: 0022-1007 |
| بيانات النشر: | Rockefeller University Press, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Time Factors, Amyloid, Immunology, BACE1-AS, Hippocampus, Mice, Transgenic, Pharmacology, Amyloid beta-Protein Precursor, Mice, Atrophy, Alzheimer Disease, medicine, Amyloid precursor protein, Animals, Humans, Immunology and Allergy, ddc:616, Dose-Response Relationship, Drug, biology, Chemistry, Alzheimer-Krankheit, Demenz, Neurologie, Morbus Alzheimer, Anti-Inflammatory Agents, Non-Steroidal, Hydrazones, Brief Definitive Report, P3 peptide, Alzheimer's disease, dementia, Cell Biology, medicine.disease, Biochemistry of Alzheimer's disease, Cell culture, biology.protein, Brief Definitive Reports, Microglia |
| الوصف: | Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid beta protein (Abeta) peptide "oligomers" and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Abeta assembly and protects neuronal cells from the toxic effect of soluble Abeta oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Abeta deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Abeta accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD. |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9492881d84d4803da2a6679061d58b52Test https://doi.org/10.1084/jem.20060467Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9492881d84d4803da2a6679061d58b52 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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