Coenzyme Q10 restores amyloid beta-inhibited proliferation of neural stem cells by activating the PI3K pathway.
Stem Cells Dev
; 22(15): 2112-20, 2013 Aug 01.
Article
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| MEDLINE
| ID: mdl-23509892
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 ß (Aß)25-35 oligomer-inhibited proliferation of NSCs by focusing on the PI3K pathway. To evaluate the effects of CoQ10 on Aß25-35 oligomer-inhibited proliferation of NSCs, NSCs were treated with several concentrations of CoQ10 and/or Aß25-35 oligomers. BrdU labeling, Colony Formation Assays, and immunoreactivity of Ki-67, a marker of proliferative activity, showed that NSC proliferation decreased with Aß25-35 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-3ß (Ser9), and heat shock transcription factor, which are proteins related to the PI3K pathway in Aß25-35 oligomers-treated NSCs. To confirm a direct role for the PI3K pathway in CoQ10-induced restoration of proliferation of NSCs inhibited by Aß25-35 oligomers, NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of CoQ10 on the proliferation of NSCs inhibited by Aß25-35 oligomers were almost completely blocked. Together, these results suggest that CoQ10 restores Aß25-35 oligomer-inhibited proliferation of NSCs by activating the PI3K pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Ubiquinona
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Fármacos Neuroprotectores
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Fosfatidilinositol 3-Quinasas
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Proliferación Celular
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Células-Madre Neurales
Límite:
Animals
Idioma:
En
Revista:
Stem Cells Dev
Asunto de la revista:
HEMATOLOGIA
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Estados Unidos