Zm. Suo et al., Phenyl-N-tert-butyl nitrone neutralizes the activities of beta-amyloid peptides in both cultured cells and isolated vessels, ALZHEIM REP, 1(6), 1998, pp. 381-387
Several lines of evidence suggest that the beta-amyloid (A beta) peptides a
re partially responsible for the pathogenesis of Alzheimer's disease (AD).
Our recent studies indicate that A beta-induced cerebral vascular dysfuncti
on may play a significant role in the development of the disease. For examp
le, A beta induces vascular endothelial cell death and enhances vasoconstri
ction. Since excess free radicals and increased cytosolic calcium have been
suggested to be involved in A beta-induced cellular and vascular dysfuncti
on, we screened several kinds of antioxidants and calcium channel modulator
s in both cultured cells and isolated vessels for their ability to prevent
these effects. We found that, while some agents could partially prevent eit
her A beta cytotoxicity or vasoactivity, a spin trapping agent, phenyl N-te
rtbutyl nitrone (PBN), completely blocks A beta-enhanced vasoconstriction a
nd protects both vascular endothelial and neuronal cells from A beta-induce
d death.