S-52, a novel nootropic compound, protects against β-amyloid induced neuronal injury by attenuating mitochondrial dysfunction.

Abstract

Accumulating evidence suggests that β-amyloid (Aβ)-induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S-52, a novel nootropic compound, on Aβ-induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S-52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S-52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ-harmed cells but also in unharmed, normal cells. The role of S-52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S-52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy.

• Authors: Xin Gao, Chun Yan Zheng, Guo Wei Qin, Xi Can Tang, Hai Yan Zhang
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 90 Issue 10 Pg. 1981-8 (Oct 2012) ISSN: 1097-4547 [Electronic] United States
• PMID: 22714678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Amyloid beta-Peptides
• Free Radical Scavengers
• Morphinans
• Nootropic Agents
• Peptide Fragments
• Reactive Oxygen Species
• S-52 compound
• amyloid beta-protein (25-35)
• Superoxides
• Hydroxyl Radical
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Amyloid beta-Peptides (antagonists & inhibitors, toxicity)
• Animals
• Cell Survival (drug effects)
• Electron Transport (drug effects)
• Fluorometry
• Free Radical Scavengers (pharmacology)
• Hydroxyl Radical (metabolism)
• Membrane Potentials (drug effects)
• Microscopy, Electron, Transmission
• Mitochondria (drug effects, metabolism, ultrastructure)
• Mitochondrial Membranes (drug effects, metabolism)
• Morphinans (pharmacology)
• Neurons (drug effects, metabolism, pathology)
• Nootropic Agents (pharmacology)
• PC12 Cells
• Peptide Fragments (antagonists & inhibitors, toxicity)
• Rats
• Reactive Oxygen Species (metabolism)
• Superoxides (metabolism)