1. Academic Validation
  2. Anatabine lowers Alzheimer's Aβ production in vitro and in vivo

Anatabine lowers Alzheimer's Aβ production in vitro and in vivo

  • Eur J Pharmacol. 2011 Nov 30;670(2-3):384-91. doi: 10.1016/j.ejphar.2011.09.019.
Daniel Paris 1 David Beaulieu-Abdelahad Corbin Bachmeier Jon Reed Ghania Ait-Ghezala Alex Bishop Jin Chao Venkat Mathura Fiona Crawford Michael Mullan
Affiliations

Affiliation

  • 1 Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rfdn.org
Abstract

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.

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