Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide （Aβ） in the brain after stroke, but...Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide （Aβ） in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-deaving enzyme 1 （BACE1）, the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 （APP695） cell models of cerebral isch- emia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin （an autophagy inducer） or 3-methyladenine （an autophagy inhibitor） on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.展开更多
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, ...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.展开更多
基金supported by the National Natural Science Foundation of China,No.31171014,31371065a grant from Shanghai Municipal Health Bureau,China,No.20134125a grant from Shanghai Pudong District Health Bureau of China,No.PDZz2013-10
文摘Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide （Aβ） in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-deaving enzyme 1 （BACE1）, the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 （APP695） cell models of cerebral isch- emia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin （an autophagy inducer） or 3-methyladenine （an autophagy inhibitor） on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.
基金the National Natural Science Foundation of China,No.30600196the Science Foundation of Chongqing,No.2006BB5042the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,No.[2007]1108
文摘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.
