37 0

Neuroprotective effects of donepezil against A beta 42-induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK-3 beta and nAChRs activity

Title
Neuroprotective effects of donepezil against A beta 42-induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK-3 beta and nAChRs activity
Author
고성호
Keywords
amyloid-beta; donepezil; GSK-3; nAChRs; neuroprotection; PP2A
Issue Date
2013-11
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF NEUROCHEMISTRY, 권: 127, 호: 4, 페이지: 562-574
Abstract
The main purpose of this study was to evaluate whether donepezil, acetylcholinesterase inhibitor, shown to play a protective role through inhibiting glycogen synthesis kinase-3 (GSK-3) activity, could also exert neuroprotective effects by stimulating protein phosphatase 2A (PP2A) activity in the amyloid-beta (A)42-induced neuronal toxicity model of Alzheimer's disease. In A42-induced toxic conditions, each PP2A and GSK-3 activity measured at different times showed time-dependent reverse pattern toward the direction of accelerating neuronal deaths with the passage of time. In addition, donepezil pre-treatment showed dose-dependent stepwise increase of neuronal viability and stimulation of PP2A activity. However, such effects on them were significantly reduced through the depletion of PP2A activity with either okadaic acid or PP2Ac siRNA. In spite of blocked PP2A activity in this A42 insult, however, donepezil pretreatment showed additional significant recovering effect on neuronal viability when compared to the value without donepezil. Moreover, donepezil partially recovered its dephosphorylating effect on hyperphosphorylated tau induced by A42. This observation led us to assume that additional mechanisms of donepezil, including its inhibitory effect on GSK-3 activity and/or the activation role of nicotinic acetylcholine receptors (nAChRs), might be involved. Taken together, our results suggest that the neuroprotective effects of donepezil against A42-induced neurotoxicity are mediated through activation of PP2A, but its additional mechanisms including regulation of GSK-3 and nAChRs activity would partially contribute to its effects.
URI
http://onlinelibrary.wiley.com/doi/10.1111/jnc.12319/abstract;jsessionid=1DAE23B21A84866F48992BE36890323E.f01t04http://hdl.handle.net/20.500.11754/50995
ISSN
0022-3042; 1471-4159
DOI
10.1111/jnc.12319
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > ETC
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE