Amyloid β-peptide (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD) brain, is hypothesized to be a key factor in the neurodegeneration seen in AD. Recently it has been shown by us and others that the neurotoxicity of Aβ occurs in conjunction with free radical oxidative stress associated with the peptide. Aβ(1-40) and several other fragments of the Aβ sequence are associated with free radicals in solution that are detectable using electron paramagnetic resonance spectroscopy. These free radicals were shown to attack brain cell membranes, initiate lipid peroxidation, increase Ca2+ influx and damage membrane and cytosolic proteins. In AD brain obtained under rapid autopsy protocol, the activity of the oxidatively-sensitive enzyme creatine kinase was shown to be significantly reduced. We reasoned that Aβ-associated free radical-induced modification of creatine kinase activity and other markers of cellular damage might be modulated by free radical scavengers. Accordingly, this study demonstrates that vitamin E can modulate Aβ(25-35)induced oxidative damage to creatine kinase and cellular proteins in cultured embryonic hippocampal neurons. These results, consistent with the hypothesis of free radical- mediated Aβ toxicity in AD, are discussed with deference to potential free radical scavengers as therapeutic agents for slowing the progression of AD.
|Number of pages||9|
|State||Published - 1999|
Bibliographical noteFunding Information:
This work was supported in part by grants from NIH (AG-10836; AG-05119). We gratefully acknowledge Dr. Mark Mattson for the use of the confocal laser scanning microscope, Dr. Kenneth Ain for the use of camera system, Dr. Anna Bruce-Keller for assistance with the ROS detection, and Dr. Marina Aksenova for technical assistance.
- Alzheimer's disease
- Creatine kinase
- Free radicals
- Protein oxidation
- Vitamin E
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience