THE aim of the present study was to determine whether amyloid beta-pep
tide (A beta) induces mitochondrial dysfunction. Mitochondrial functio
n was reported to be affected following A beta exposure, as demonstrat
ed by depolarization of the mitochondrial membrane, decrease of oxygen
consumption and by the inhibition of complexes I, III and IV of the m
itochondrial respiratory chain. A beta 25-35 and A beta 1-40 peptides
also inhibited MTT reduction in a dose-dependent manner in undifferent
iated and differentiated PC12 cells. Several antioxidants prevented th
is inhibitory response, suggesting that oxidative stress is involved i
n A beta-induced cytotoxicity. These data suggest that mitochondrial d
ysfunction contributes to amyloid beta-protein cytotoxicity and may pl
ay a major role in the abnormalities of energy metabolism observed in
Alzheimer's disease. (C) 1998 Rapid Science Ltd.