amyloid-beta-peptides and idebenone

Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown that A beta peptides (A beta25-35 and A beta1-40) induce a concentration-dependent accumulation of reactive oxygen species (ROS), decrease the cellular redox activity, and lead to the depletion of ATP levels. The observed inhibition by A beta of mitochondrial function and of glycolysis is blocked by the antioxidants vitamin E, idebenone, and GSH ethyl ester. Taken together, these data suggest that exposure of PC12 cells to A beta results in an impairment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability. Furthermore, the generation of ROS seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta.

Topics: Adenosine Triphosphate; Amyloid beta-Peptides; Animals; Antioxidants; Benzoquinones; Deoxyglucose; Dose-Response Relationship, Drug; Electron Transport; Electron Transport Complex II; Electron Transport Complex III; Electron Transport Complex IV; Glutathione; Glycolysis; Mitochondria; Multienzyme Complexes; NAD(P)H Dehydrogenase (Quinone); Neurons; Neuroprotective Agents; Oxidative Stress; Oxidoreductases; PC12 Cells; Peptide Fragments; Pyruvic Acid; Rats; Succinate Dehydrogenase; Tritium; Ubiquinone; Vitamin E