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Coenzyme Q10 Restores Amyloid Beta-Inhibited Proliferation of Neural Stem Cells by Activating the PI3K Pathway

Title
Coenzyme Q10 Restores Amyloid Beta-Inhibited Proliferation of Neural Stem Cells by Activating the PI3K Pathway
Author
고성호
Keywords
SYNTHASE KINASE 3-BETA; ALZHEIMERS-DISEASE; INDUCED NEUROTOXICITY; SUBVENTRICULAR ZONE; NEUROGENESIS; PERSPECTIVE; MEMORY; MODEL; MICE; AGE
Issue Date
2013-04
Publisher
Mary Ann Liebert
Citation
Stem Cells and Development, April 2013, 22(15), P.2112-2120
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 beta (A beta)(25-35) oligomer-inhibited proliferation of NSCs by focusing on the PI3K pathway. To evaluate the effects of CoQ10 on A beta(25-35) oligomer-inhibited proliferation of NSCs, NSCs were treated with several concentrations of CoQ10 and/or A beta(25-35) oligomers. BrdU labeling, Colony Formation Assays, and immunoreactivity of Ki-67, a marker of proliferative activity, showed that NSC proliferation decreased with A beta(25-35) oligomer treatment, but combined treatment with CoQ10 restored it. Western blotting showed that CoQ10 treatment increased the expression levels of p85 alpha PI3K, phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3 beta (Ser9), and heat shock transcription factor, which are proteins related to the PI3K pathway in A beta(25-35) oligomers-treated NSCs. To confirm a direct role for the PI3K pathway in CoQ10-induced restoration of proliferation of NSCs inhibited by A beta(25-35) oligomers, NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of CoQ10 on the proliferation of NSCs inhibited by A beta(25-35) oligomers were almost completely blocked. Together, these results suggest that CoQ10 restores A beta(25-35) oligomer-inhibited proliferation of NSCs by activating the PI3K pathway.
URI
http://online.liebertpub.com/doi/abs/10.1089/scd.2012.0604http://hdl.handle.net/20.500.11754/44151
ISSN
1547-3287
DOI
10.1089/scd.2012.0604
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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