Alzheimer’s disease(AD)is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly.Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pat...Alzheimer’s disease(AD)is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly.Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD.Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear,the current treatments are those drugs that can alleviate the symptoms of AD patients.Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation.Thus the pharmacological mechanism of these drugs may be too simply-evaluated.This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.展开更多
Background:Several studies indicated that Erythropoietin(Epo)may provide remarkable neuroprotection in some neurological diseases.It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex ...Background:Several studies indicated that Erythropoietin(Epo)may provide remarkable neuroprotection in some neurological diseases.It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats,suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD.Methods:The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta.The viability of the cells,the apoptosis of the cells and the level of Bax,Bcl-2,cleaved caspase-3 and cleaved PARP expression were detected by MTT,Hoechst 33258 staining and Western blotting respectively.Results:20μM Abeta(25-35)could induce a decreased viability and a increased apoptosis in PC12 cell in a timedependent manner.However,20μM Abeta(35-25)had no effect on cell viability and apoptosis.Western blot analysis also showed that Abeta(25-35)treatment could decrease the expression of Bcl-2(P<0.05)and increase the expression of Bax(P<0.05),Cleaved casapase-3(P<0.05),and Cleaved PARP(P<0.05).The pretreatment of Epo could effectively reverse all the above changes induced by Abeta_((25-35))(P<0.05).Furthermore,the protective effect of Epo could be blocked by PI3K inhibitor LY294002(P<0.05).Conclusions:Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35)and this effect may depend on the PI3K⁄Akt pathway.Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer’s disease.展开更多
基金This study was supported by grants from the State Key Basic Research Program(No.2010CB945200)National"Twelfth Five-Year"Plan for Science&Technology Support(2012BAI10B03)+2 种基金Program for Outstanding Medical Academic Leader(No.LJ 06003)Shanghai Jiao Tong University Medical and Engineering Joint Key Project(No.YG2010ZD102)Henan Key Science and Technology Project(No.112102310684).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly.Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD.Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear,the current treatments are those drugs that can alleviate the symptoms of AD patients.Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation.Thus the pharmacological mechanism of these drugs may be too simply-evaluated.This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.
基金This study was supported by grants from the State Key Basic Research Program(No.2010CB945200)Shanghai Key Discipline Program(No.S30202)+2 种基金Shanghai Natural Scientific Fund(No.09JC1416402,09ZR1419100)Program for Outstanding Medical Academic Leader(No.LJ 06003)Shanghai Jiao Tong University Medical and Engineering Joint Key Project(No.YG2010ZD102).
文摘Background:Several studies indicated that Erythropoietin(Epo)may provide remarkable neuroprotection in some neurological diseases.It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats,suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD.Methods:The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta.The viability of the cells,the apoptosis of the cells and the level of Bax,Bcl-2,cleaved caspase-3 and cleaved PARP expression were detected by MTT,Hoechst 33258 staining and Western blotting respectively.Results:20μM Abeta(25-35)could induce a decreased viability and a increased apoptosis in PC12 cell in a timedependent manner.However,20μM Abeta(35-25)had no effect on cell viability and apoptosis.Western blot analysis also showed that Abeta(25-35)treatment could decrease the expression of Bcl-2(P<0.05)and increase the expression of Bax(P<0.05),Cleaved casapase-3(P<0.05),and Cleaved PARP(P<0.05).The pretreatment of Epo could effectively reverse all the above changes induced by Abeta_((25-35))(P<0.05).Furthermore,the protective effect of Epo could be blocked by PI3K inhibitor LY294002(P<0.05).Conclusions:Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35)and this effect may depend on the PI3K⁄Akt pathway.Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer’s disease.
