title: Local anesthetic procaine protects rat pheochromocytoma PC12 cells against beta-amyloid-induced neurotoxicity.
abstract: 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.affiliation: Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20057, USA. ll55@georgetown.edu
authors.forename: Laurent
authors.initials: L
authors.lastname: Lecanu
authors.forename: Yao
authors.initials: Y
authors.lastname: Wenguo
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Janet
authors.initials: J
authors.lastname: Greeson
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010673:Pheochromocytoma / Q000473:pathology; D011343:Procaine / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000779:Anesthetics, Local; D005609:Free Radicals; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011955:Receptors, Drug; D016194:Receptors, N-Methyl-D-Aspartate; D018013:Receptors, Neuropeptide; D015222:Sodium Channels; C075222:amyloid beta-protein (1-42); D011343:Procaine; D000255:Adenosine Triphosphate; D006903:Hydroxymethylglutaryl CoA Reductases