科研之友
微信
新浪微博
Facebook
分享链接
摘要
The entangled relationship of brain aging, mitochondrial dysfunction, and amyloid-beta peptide (A beta(42)) toxicity occupies the center stage in the pathogenesis of Alzheimer's disease (AD). The present study examines some of the toxic effects of A beta(42) on brain mitochondria and provides evidence that aged brain mitochondria are significantly more vulnerable to A beta(42) toxicity. In particular, the study has shown that the aggregated, but not the monomeric, form of A beta(42) in varying concentrations (10-40 mu M) during in vitro incubation causes a loss of mitochondrial membrane potential, a decrease in phosphorylation capacity and ATP synthesis, and the release of cytochrome c from the mitochondria but without any noticeable change in the activities of respiratory chain complexes. Such effects of A beta(42) are strikingly more conspicuous on aged rat (22-24 months) brain mitochondria compared to that on brain mitochondria of young rats (4-6 months). More interesting is the observation that in contrast to young rat brain mitochondria, a significantly higher level of A beta(42) remains associated with aged brain mitochondria under basal incubation condition as well as after exposure to exogenously added peptide. Extrapolated to an in vivo scenario, the results have clear implications in AD pathogenesis and also partly explain why brain aging is a dominant risk factor for this disease condition.
- 出版日期2011
