Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

Anatabine lowers Alzheimer's Aß production in vitro and in vivo. published in NCBI Pubmed.com US National Library of Medicine National Institutes of Health, Paris D1, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M. Roskamp Institute, 2040 Whit?eld Avenue, Sarasota, FL 34243, USA

Abstract:
Brain Aß 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 Aß 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 Aß1?40 and Aß1?42 levels in a dose dependent manner and reduces sAPPß production without impacting sAPPa levels suggesting that anatabine lowers Aß production by mainly impacting the ß-cleavage of APP. Additionally, we show that anatabine lowers NF?B activation at doses that inhibit Aß production in vitro. Since NF?B is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aß 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 Aß 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 Aß1?40 and Aß1?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 Aß accumulation.

Published before at Investohub but noted again.
Article at:
http://www.ncbi.nlm.nih.gov/pubmed/21958873