Document Detail


Galantamine inhibits calpain-calcineurin signaling activated by beta-amyloid in human neuroblastoma SH-SY5Y cells.
MedLine Citation:
PMID:  20665950     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Galantamine, which is currently used in the treatment of patients with Alzheimer's disease (AD), has been shown to have a neuroprotective effect against beta-amyloid (Abeta) peptide-induced toxicity, which is involved in the pathogenesis of AD. In this study, we investigated the mechanism underlying the protective effect of galantamine on Abeta-induced toxicity in human neuroblastoma cells (SH-SY5Y). Using MTT and LDH leakage assays, we observed that galantamine pretreatment significantly prevented Abeta1-40-induced cell death. Abeta1-40-induced overexpression and increased cleavage of both calpain and calcineurin were observed by Western blotting and double immunofluorescent staining. Increased calcineurin phosphatase activity and decreased level of pSer112 BAD were also observed in Abeta1-40-damaged cells. However, all these alterations were found to be reversed by galantamine pretreatment. We also found that the neuroprotection of galantamine can be blocked by an alpha7 nAChR antagonist. Overall, our results suggest that galantamine may prevent the neuronal damage induced by Abeta1-40 through a mechanism related to the regulation of calpain-calcineurin activation and BAD phosphorylation, which may involve the participation of alpha7 nAChR.
Authors:
Qianqian Li; Jing Fang; Meimei Yang; Donglai Wu; Liming Zhang; Yan Zhang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience letters     Volume:  480     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  173-7     Citation Subset:  IM    
Affiliation:
Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin, PR China.
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