HauptinhaltErfahrungen zu Sammeln,Eigentuemlichkeiten zu Entwickeln,Neue TreppeHinaufzugehen——Zustand und Entwicklung des Arbeitstechnikunterrichtsder Mittelschulen in SuzhouSchrittweise Erhoehung,Systematische Entw...HauptinhaltErfahrungen zu Sammeln,Eigentuemlichkeiten zu Entwickeln,Neue TreppeHinaufzugehen——Zustand und Entwicklung des Arbeitstechnikunterrichtsder Mittelschulen in SuzhouSchrittweise Erhoehung,Systematische Entwicklung——ElementarcForschung nach der Richtung der Arbeitstechnikerziehung in Jiangsu。展开更多
Alzheimer’s disease(AD)is characterized by senile plaques(SP)composed of b-amyloid protein(Ab)and neurofibrillary tangles(NFTs)composed of intracellular hyperphosphorylated tau.Recently,nuclear receptor subfamily 4 g...Alzheimer’s disease(AD)is characterized by senile plaques(SP)composed of b-amyloid protein(Ab)and neurofibrillary tangles(NFTs)composed of intracellular hyperphosphorylated tau.Recently,nuclear receptor subfamily 4 group A member 1(NR4A1)was implicated in synaptic plasticity,long-term memory formation,suggesting that it may play a role in the pathophysiology of AD.Here,we showed that the expression of NR4A1 was significantly increased in the hippocampus of APP/PS1 transgenic mice.In addition,NR4A1 overexpression in HT22 cells up-regulated APP and BACE1 levels,down-regulated ADAM10 expression,and promoted amyloidogenesis as indicated by decreased a-CTF levels and elevated b-CTF levels.Furthermore,a raised level of phospho-tau(p-tau,S396)was accompanied by p-GSK3b(S9)expression reducing,but total tau,p-tau(S262 and T231),CDK5 and ERK remained unchanged in NR4A1-overexpressing cells.Collectively,our results suggest that NR4A1 promotes the amyloidogenic processing of APP by regulating ADAM10 and BACE1 expression in HT22 cells;as well as NR4A1 accelerates tau hyperphosphorylation by GSK3b signal.Therefore,NR4A1 may play an important role in the pathogenesis of AD.展开更多
文摘HauptinhaltErfahrungen zu Sammeln,Eigentuemlichkeiten zu Entwickeln,Neue TreppeHinaufzugehen——Zustand und Entwicklung des Arbeitstechnikunterrichtsder Mittelschulen in SuzhouSchrittweise Erhoehung,Systematische Entwicklung——ElementarcForschung nach der Richtung der Arbeitstechnikerziehung in Jiangsu。
基金This study was supported by the National Natural Science Foundation of China(grant numbers:31500821).
文摘Alzheimer’s disease(AD)is characterized by senile plaques(SP)composed of b-amyloid protein(Ab)and neurofibrillary tangles(NFTs)composed of intracellular hyperphosphorylated tau.Recently,nuclear receptor subfamily 4 group A member 1(NR4A1)was implicated in synaptic plasticity,long-term memory formation,suggesting that it may play a role in the pathophysiology of AD.Here,we showed that the expression of NR4A1 was significantly increased in the hippocampus of APP/PS1 transgenic mice.In addition,NR4A1 overexpression in HT22 cells up-regulated APP and BACE1 levels,down-regulated ADAM10 expression,and promoted amyloidogenesis as indicated by decreased a-CTF levels and elevated b-CTF levels.Furthermore,a raised level of phospho-tau(p-tau,S396)was accompanied by p-GSK3b(S9)expression reducing,but total tau,p-tau(S262 and T231),CDK5 and ERK remained unchanged in NR4A1-overexpressing cells.Collectively,our results suggest that NR4A1 promotes the amyloidogenic processing of APP by regulating ADAM10 and BACE1 expression in HT22 cells;as well as NR4A1 accelerates tau hyperphosphorylation by GSK3b signal.Therefore,NR4A1 may play an important role in the pathogenesis of AD.
