title: Coenzyme Q10 restores amyloid beta-inhibited proliferation of neural stem cells by activating the PI3K pathway.
abstract: Neurogenesis in the adult brain is important for memory and learning, and the alterations in neural stem cells (NSCs) may be an important part of Alzheimer's disease pathogenesis. The phosphatidylinositol 3-kinase (PI3K) pathway has been suggested to play an important role in neuronal cell survival and is highly involved in adult neurogenesis. Recently, coenzyme Q10 (CoQ10) was found to affect the PI3K pathway. We investigated whether CoQ10 could restore amyloid β (Aβ)25-35 oligomer-inhibited proliferation of NSCs by focusing on the PI3K pathway. To evaluate the effects of CoQ10 on Aβ25-35 oligomer-inhibited proliferation of NSCs, NSCs were treated with several concentrations of CoQ10 and/or Aβ25-35 oligomers. BrdU labeling, Colony Formation Assays, and immunoreactivity of Ki-67, a marker of proliferative activity, showed that NSC proliferation decreased with Aβ25-35 oligomer treatment, but combined treatment with CoQ10 restored it. Western blotting showed that CoQ10 treatment increased the expression levels of p85α PI3K, phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3β (Ser9), and heat shock transcription factor, which are proteins related to the PI3K pathway in Aβ25-35 oligomers-treated NSCs. To confirm a direct role for the PI3K pathway in CoQ10-induced restoration of proliferation of NSCs inhibited by Aβ25-35 oligomers, NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of CoQ10 on the proliferation of NSCs inhibited by Aβ25-35 oligomers were almost completely blocked. Together, these results suggest that CoQ10 restores Aβ25-35 oligomer-inhibited proliferation of NSCs by activating the PI3K pathway.
authors.affiliation: Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Hojin
authors.initials: H
authors.lastname: Choi
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Park
authors.forename: Kyu-Yong
authors.initials: KY
authors.lastname: Lee
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Choi
authors.forename: Hyun-Jeung
authors.initials: HJ
authors.lastname: Yu
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jinse
authors.initials: J
authors.lastname: Park
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014451:Ubiquinone; D019869:Phosphatidylinositol 3-Kinases; C024989:coenzyme Q10