Low dose nicotine attenuates Aβ neurotoxicity through activation early growth response gene 1 pathway.

Abstract

Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity. Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35). This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.