کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829953 | 1559012 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Anatabine lowers Alzheimer's Aβ production in vitro and in vivo
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Brain Aβ accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aβ production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aβ1-40 and Aβ1-42 levels in a dose dependent manner and reduces sAPPβ production without impacting sAPPα levels suggesting that anatabine lowers Aβ production by mainly impacting the β-cleavage of APP. Additionally, we show that anatabine lowers NFκB activation at doses that inhibit Aβ production in vitro. Since NFκB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aβ production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aβ lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aβ1-40 and Aβ1-42 levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aβ accumulation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 384-391
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 384-391
نویسندگان
Daniel Paris, David Beaulieu-Abdelahad, Corbin Bachmeier, Jon Reed, Ghania Ait-Ghezala, Alex Bishop, Jin Chao, Venkat Mathura, Fiona Crawford, Michael Mullan,