Abstract |
Oxidative stress-mediated neuronal death may be initiated by a decrease in glutathione (GSH), whose levels are reduced in mitochondrial and synaptosomal fractions of specific CNS regions in Alzheimer disease (AD) patients. Currently, the use of GSH as a therapeutic agent is limited by its unfavorable pharmacokinetic properties. In this study, we designed the synthesis of new S-acyl glutathione (acyl-SG) thioesters of fatty acids via N-acyl benzotriazole-intermediate production and investigated their potential for targeted delivery of the parent GSH and free fatty acid to amyloid-exposed fibroblasts from familial AD patients and human SH-SY5Y neuroblastoma cells. Cell culture supplementation with acyl-SG derivatives triggers a significant decrease in lipid peroxidation and mitochondrial dysfunction in a fatty acid unsaturation degree-dependent fashion. Acyl-SG thioesters also protect cholinergic neurons against Aβ-induced damage and reduce glial reaction in rat brains. Collectively, these findings suggest that acyl-SG thioesters could prove useful as a tool for controlling AD-induced cerebral deterioration.
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Authors | Mariagioia Zampagni, Daniel Wright, Roberta Cascella, Giampiero D'Adamio, Fiorella Casamenti, Elisa Evangelisti, Francesca Cardona, Andrea Goti, Benedetta Nacmias, Sandro Sorbi, Gianfranco Liguri, Cristina Cecchi |
Journal | Free radical biology & medicine
(Free Radic Biol Med)
Vol. 52
Issue 8
Pg. 1362-71
(Apr 15 2012)
ISSN: 1873-4596 [Electronic] United States |
PMID | 22326489
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Amyloid
- Receptors, Cholinergic
- Caspase 3
- Glutathione
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Topics |
- Amyloid
(metabolism)
- Animals
- Brain
(drug effects, pathology)
- Caspase 3
(metabolism)
- Cell Line, Tumor
- Cells, Cultured
- Enzyme Activation
- Fluorescent Antibody Technique
- Glutathione
(pharmacology)
- Humans
- Models, Biological
- Oxidative Stress
(drug effects)
- Rats
- Receptors, Cholinergic
(metabolism)
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