Document Detail


The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.
MedLine Citation:
PMID:  20218980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress.
EXPERIMENTAL APPROACH: We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated.
KEY RESULTS: Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam.
CONCLUSION AND IMPLICATIONS: Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.
Authors:
C Kurz; I Ungerer; U Lipka; S Kirr; T Schütt; A Eckert; K Leuner; W E Müller
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-09
Journal Detail:
Title:  British journal of pharmacology     Volume:  160     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-28     Completed Date:  2010-06-02     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  246-57     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Biocenter, University Frankfurt/M, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / biosynthesis
Amyloid beta-Peptides / metabolism,  secretion
Amyloid beta-Protein Precursor / metabolism
Animals
Brain / cytology,  drug effects
Cell Line
Humans
Membrane Potential, Mitochondrial / drug effects*
Mice
Neurites / drug effects,  metabolism
Neuroprotective Agents / pharmacology*
Oxidative Stress / drug effects*
PC12 Cells
Peptide Fragments / metabolism
Piracetam / pharmacology*
Rats
Transfection
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Neuroprotective Agents; 0/Peptide Fragments; 0/amyloid beta-protein (1-42); 56-65-5/Adenosine Triphosphate; 7491-74-9/Piracetam
Comments/Corrections
Comment In:
Br J Pharmacol. 2010 May;160(2):217-9   [PMID:  20423336 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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