Curcumin inhibits Aß-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways.

ABSTRACT

Amyloid ß (Aß) plays an important role in Alzheimer's disease (AD) by inducing microglia activation. Once activated, microglial cells promote the release of reactive species and cytokines that are known to enhance immune responses in AD brain. Thus, negative regulators of microglia activation are considered as potential therapeutic candidates for AD. Curcumin, the major yellow pigment in turmeric (Curcuma longa), is proposed for its anti-inflammatory properties. Several studies have indicated the suppressive effects of curcumin on LPS-induced microglia activation and MAPK activities. However, the effects of curcumin on Aß-treated microglia and the possible mechanisms are still not fully understood. In the present study, we found that curcumin improved microglial viability against Aß42 in a time- and dose-dependent manner and remarkably suppressed Aß42-induced CD68 expression. Moreover, curcumin concentration-dependently abolished Aß42-induced interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in mRNA and protein levels in microglia. Besides, curcumin exerted an inhibitory effect on phosphorylation of ERK1/2 and p38 in Aß42-activated microglia. Further experiments indicated that blockage of ERK1/2 and p38 pathways reduced inflammatory cytokines production from microglia. These results show that curcumin suppresses ERK1/2 and p38 signaling, thus, attenuating inflammatory responses of brain microglia.