摘要
Several studies have demonstrated that the amount of beta-amyloid （Aβ） protein in the brain can be lowered by down-regulating Aβ production, promoting Aβ degradation, reducing Aβ oligomerization or deposition, thereby alleviating symptoms of Alzheimer＇s disease. Curcumin has been known to be a peroxisome proliferator activated receptor gamma （PPARy） agonist and can obviously inhibit Aβ production and oligomerization. This study investigated the effects of curcumin on the G-site APP cleaving enzyme 1 （BACE1） activity and PPARy expression in human neuroblastoma SH-SY5Y cells, and validated the inhibitory effects of curcumin on Aβ40/42 expression in the brain. Results revealed that PPARy mRNA and protein expression in the human neuroblastoma SH-SY5Y cells significantly increased with increasing curcumin concentration and time course （P 〈 0.05）; BACE1 mRNA and protein expression and Aβ40/42 production significantly decreased with increasing curcumin concentration and time course （P 〈 0.05）. The changes in PPARy and BACE1 expression during Aβ production could be reversed by the PPARy antagonist GW9662. These findings indicate that curcumin reduced Aβ production by activating PPARy expression and inhibiting BACE1 expression in a concentration- and time-dependent manner.
Several studies have demonstrated that the amount of beta-amyloid （Aβ） protein in the brain can be lowered by down-regulating Aβ production, promoting Aβ degradation, reducing Aβ oligomerization or deposition, thereby alleviating symptoms of Alzheimer＇s disease. Curcumin has been known to be a peroxisome proliferator activated receptor gamma （PPARy） agonist and can obviously inhibit Aβ production and oligomerization. This study investigated the effects of curcumin on the G-site APP cleaving enzyme 1 （BACE1） activity and PPARy expression in human neuroblastoma SH-SY5Y cells, and validated the inhibitory effects of curcumin on Aβ40/42 expression in the brain. Results revealed that PPARy mRNA and protein expression in the human neuroblastoma SH-SY5Y cells significantly increased with increasing curcumin concentration and time course （P 〈 0.05）; BACE1 mRNA and protein expression and Aβ40/42 production significantly decreased with increasing curcumin concentration and time course （P 〈 0.05）. The changes in PPARy and BACE1 expression during Aβ production could be reversed by the PPARy antagonist GW9662. These findings indicate that curcumin reduced Aβ production by activating PPARy expression and inhibiting BACE1 expression in a concentration- and time-dependent manner.
基金
the National Natural Science Foundation of China,No.30600196
the Science Foundation of Chongqing,No.2006BB5042
the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,No.[2007]1108
