Document Detail


Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (-)-epigallocatechin-3-gallate.
MedLine Citation:
PMID:  21434871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-D-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(-)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD.
Authors:
Yan He; Jiankun Cui; James C-M Lee; Shinghua Ding; Malgorzata Chalimoniuk; Agnes Simonyi; Albert Y Sun; Zezong Gu; Gary A Weisman; W Gibson Wood; Grace Y Sun
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-02-08
Journal Detail:
Title:  ASN neuro     Volume:  3     ISSN:  1759-0914     ISO Abbreviation:  ASN Neuro     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-25     Completed Date:  2011-06-10     Revised Date:  2014-07-29    
Medline Journal Info:
Nlm Unique ID:  101507115     Medline TA:  ASN Neuro     Country:  Unknown    
Other Details:
Languages:  eng     Pagination:  e00050     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Peptides / pharmacology*
Analysis of Variance
Animals
Arachidonic Acid / metabolism
Calcium / metabolism
Catechin / analogs & derivatives*,  pharmacology
Cell Survival / drug effects
Cells, Cultured
Cerebral Cortex / cytology*
Drug Interactions
Embryo, Mammalian
Glycoproteins / pharmacology
L-Lactate Dehydrogenase / metabolism
N-Methylaspartate / pharmacology
NADPH Oxidase / antagonists & inhibitors,  metabolism*
Neurons / drug effects*
Neuroprotective Agents / pharmacology*
Oxazines / diagnostic use
Peptide Fragments / pharmacology*
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Receptors, N-Methyl-D-Aspartate / metabolism*
Signal Transduction / drug effects
Tetrazolium Salts / diagnostic use
Thiazoles / diagnostic use
Time Factors
Xanthenes / diagnostic use
Grant Support
ID/Acronym/Agency:
1P50 AT006273/AT/NCCAM NIH HHS; 2P01 AG018357/AG/NIA NIH HHS; P50 AT006273/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Glycoproteins; 0/Neuroprotective Agents; 0/Oxazines; 0/Peptide Fragments; 0/Reactive Oxygen Species; 0/Receptors, N-Methyl-D-Aspartate; 0/Tetrazolium Salts; 0/Thiazoles; 0/Xanthenes; 0/amyloid beta-protein (1-42); 0/gp91ds-tat protein, chimeric; 27YG812J1I/Arachidonic Acid; 298-93-1/thiazolyl blue; 550-82-3/resazurin; 6384-92-5/N-Methylaspartate; 8R1V1STN48/Catechin; BQM438CTEL/epigallocatechin gallate; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.6.3.1/NADPH Oxidase; SY7Q814VUP/Calcium
Comments/Corrections

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