Document Detail


Local anesthetic procaine protects rat pheochromocytoma PC12 cells against beta-amyloid-induced neurotoxicity.
MedLine Citation:
PMID:  15687733     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alzheimer's disease (AD) is the most common dementia occurring in elderly. We report herein the neuroprotective properties of procaine and other anesthetic agents against beta-amyloid-induced neurotoxicity. Procaine displayed strong neuroprotective properties against the amyloid peptide Abeta(1-42) and preserved Abeta(1-42)-induced ATP depletion on rat pheochromocytoma PC12 cells. Procaine also inhibited the neurotoxic effect that glutamate displayed on PC12 cells, suggesting that the reduction of glutamate-induced neurotoxicity may be the mechanism by which these compounds exert their 'antiamyloid' effects. In search of a mechanism of action we observed that procaine is a ligand for the sigma1 receptor, a protein which ligands have been shown to protect mitochondrial function and to exert antidepressant properties. Procaine binds also to muscarinic receptors but the true meaning of this feature needs to be clarified. In conclusion, these data suggest that procaine exerts neuroprotective properties and may serve either as a treatment for AD or as a starting point for the development of novel therapies for AD.
Authors:
Laurent Lecanu; Yao Wenguo; Jing Xu; Janet Greeson; Vassilios Papadopoulos
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Publication Detail:
Type:  Journal Article     Date:  2005-01-06
Journal Detail:
Title:  Pharmacology     Volume:  74     ISSN:  0031-7012     ISO Abbreviation:  Pharmacology     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-31     Completed Date:  2005-08-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  65-78     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 S. Karger AG, Basel.
Affiliation:
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20057, USA. ll55@georgetown.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Amyloid beta-Protein / toxicity*
Anesthetics, Local / pharmacology*
Animals
Binding Sites
Cell Survival / drug effects
Free Radicals / metabolism
Hydroxymethylglutaryl CoA Reductases / biosynthesis
Neuroprotective Agents / pharmacology*
PC12 Cells
Peptide Fragments / toxicity*
Pheochromocytoma / pathology
Procaine / pharmacology*
Radioligand Assay
Rats
Receptors, Drug / metabolism
Receptors, N-Methyl-D-Aspartate / metabolism
Receptors, Neuropeptide / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sodium Channels / metabolism
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Anesthetics, Local; 0/Free Radicals; 0/Neuroprotective Agents; 0/Peptide Fragments; 0/Receptors, Drug; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Neuropeptide; 0/Sodium Channels; 0/amyloid beta-protein (1-42); 56-65-5/Adenosine Triphosphate; 59-46-1/Procaine; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases

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


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