title: Upregulation of AKT attenuates amyloid-β-induced cell apoptosis.
abstract: Overproduction and accumulation of amyloid-β (Aβ) have been proposed to be an initiating factor of neuron loss in Alzheimer's disease (AD). AKT is a pivotal molecule in regulating neuronal survival, however, it is still not known whether upregulation of AKT can protect the cells from the Aβ-induced apoptosis. By using cell viability assay and flow cytometry, we demonstrated in the present study that overexpression of AKT could significantly attenuate the cell apoptosis induced by Aβ1-42, whereas simultaneous inhibition of PI3 K, the immediate upstream stimulator of AKT, abolished the protective effect of AKT in HEK293 cells. Upregulation of AKT restored the Aβ-induced alterations of the mitochondria-related Bcl-2 family members (including Bcl-xL, Bcl-w, Bad, and Bax) and suppressed the activation of caspase-3 and JNK. Our data suggest that upregulation of AKT could be a promising therapeutic strategy for arresting Aβ toxicity in AD patients.
authors.affiliation: Department of Pathophysiology, the Key Laboratory of Neurological Diseases of the Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Qu
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Zhou
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012844:Sincalide / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D000077191:Wortmannin; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000730:Androstadienes; D017304:Annexin A5; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D012844:Sincalide; D000077191:Wortmannin