title: PI3K/AKT/mTOR/p70S6K Pathway Is Involved in Aβ25-35-Induced Autophagy.
abstract: Disruption or deregulation of the autophagy system has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Aβ plays an important role in this autophagic system. In many cases, autophagy is regulated by the phosphatidylinositol 3-phosphate kinase/AKT/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway. However, whether this signaling pathway is involved in Aβ-induced autophagy in neuronal cells is not known. Here, we studied whether Aβ25-35 induces autophagy in HT22 cells and C57 mice and investigated whether PI3K is involved in the autophagy induction. We found that Aβ25-35 inhibited HT22 cell viability in a dose- and time-dependent manner. Aβ25-35 induced autophagosome formation, the conversion of microtubule-associated protein light chain 3 (LC3), and the suppression of the mTOR pathway both in vitro and in vivo. Furthermore, Aβ25-35 impaired the learning abilities of C57 mice. Our study suggests that Aβ25-35 induces autophagy and the PI3K/AKT/mTOR/p70S6K pathway is involved in the process, which improves our understanding of the pathogenesis of AD and provides an additional model for AD research.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Shengnuo
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Medical School, Shenzhen University, Shenzhen, Guangdong 518060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luan
authors.affiliation: Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Department of Neurology, Houjie Hospital, Dongguan 511711, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C074636:amyloid beta-protein (25-35); C546842:MTOR protein, human