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
Objective： To investigate the effect and molecular mechanism of Tiantai No.1 （天泰1号）, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides （Ab...Objective： To investigate the effect and molecular mechanism of Tiantai No.1 （天泰1号）, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides （Abeta） in vitro and its effects on nuclear factor-κB （NF-κB） and cAMP responsive element-binding protein （CREB） pathways using the gene transfection technique. Methods： B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 （Aβ 1-40, 10 μmol/L） for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 （Aβ 25-35） for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 （5 μmo/L） for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results： Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta （P〈0.05, P〈0.01）. With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells （P〈0.05, P〈0.01）. Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression （P〈0.01）. Conclusions： Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.展开更多
目的研究银杏叶提取物(Extracts of ginkgo b iloba leaves,EGB)对β淀粉样蛋白(Aβ25-35)诱导的PC12细胞损伤的保护作用。方法用Aβ25-35处理诱导体外培养的PC12细胞损伤,并用EGB进行保护,显微观察细胞形态的改变,LDH法和MTT法检测细...目的研究银杏叶提取物(Extracts of ginkgo b iloba leaves,EGB)对β淀粉样蛋白(Aβ25-35)诱导的PC12细胞损伤的保护作用。方法用Aβ25-35处理诱导体外培养的PC12细胞损伤,并用EGB进行保护,显微观察细胞形态的改变,LDH法和MTT法检测细胞膜的损伤情况。结果EGB处理组细胞数比损伤组显著增多,受损变圆的细胞数较少,细胞形态明显改善,EGB处理组上清液LDH活性显著低于Aβ25-35处理组(P<0.01),MTT值显著高于Aβ25-35处理组(P<0.01)。结论EGB对Aβ25-35诱导的PC12细胞损伤具有显著的保护作用。展开更多
High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator ...High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach.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.
文摘Objective： To investigate the effect and molecular mechanism of Tiantai No.1 （天泰1号）, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides （Abeta） in vitro and its effects on nuclear factor-κB （NF-κB） and cAMP responsive element-binding protein （CREB） pathways using the gene transfection technique. Methods： B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 （Aβ 1-40, 10 μmol/L） for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 （Aβ 25-35） for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 （5 μmo/L） for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results： Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta （P〈0.05, P〈0.01）. With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells （P〈0.05, P〈0.01）. Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression （P〈0.01）. Conclusions： Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.
文摘目的研究银杏叶提取物(Extracts of ginkgo b iloba leaves,EGB)对β淀粉样蛋白(Aβ25-35)诱导的PC12细胞损伤的保护作用。方法用Aβ25-35处理诱导体外培养的PC12细胞损伤,并用EGB进行保护,显微观察细胞形态的改变,LDH法和MTT法检测细胞膜的损伤情况。结果EGB处理组细胞数比损伤组显著增多,受损变圆的细胞数较少,细胞形态明显改善,EGB处理组上清液LDH活性显著低于Aβ25-35处理组(P<0.01),MTT值显著高于Aβ25-35处理组(P<0.01)。结论EGB对Aβ25-35诱导的PC12细胞损伤具有显著的保护作用。
文摘High levels of the neurotoxic beta-amyloid protein (A<em>β</em>) in patients with Alzheimer’s disease present a significant therapeutic target, although the protein is unlikely to be the sole instigator of this condition. A<em>β</em> initiates cell receptor and synapse dysfunction, and causes mitochondrial damage within neurons. Neurotransmitters and various small molecular weight compounds ameliorate the effects of A<em>β</em> on cell membranes. This study uses a molecular modeling technique to compare the structures of A<em>β</em>25-35 and compounds known to antagonize properties of the polypeptide. Compounds provide good fits to the peptide amino acid residues, revealing planarity in their linear structures and fitting points. Compounds and polypeptide share relative molecular similarity, affinity for receptors and apoptosis modulating properties indicative of their potential for competition at neuron membrane sites. The therapeutic targeting of A<em>β</em> by small molecular weight compounds may benefit from a multi-drug approach.
