The mechanism for heme to prevent A(1-40) aggregation and its cytotoxicity.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
The -amyloid peptide (A) aggregation in the brain, known as amyloid plaques, is a hallmark of Alzheimer's disease (AD). The aberrant interaction of Cu(2+) ion with A potentiates AD by inducing A aggregation and generating neurotoxic reactive oxygen species (ROS). In this study, the biosynthesized recombinant A(1-40) was, for the first time, used to investigate the mechanism for heme to prevent A(1-40) aggregation and its cytotoxicity. Cell viability studies of SH-SY5Y cells and rat primary hippocampal neurons showed that exogenous heme can protect the cells by reducing cytotoxicity in the presence of Cu(2+) and/or A(1-40). UV-vis spectroscopy, circular dichroism spectroscopy, and differential pulse voltammetry were applied to examine the interaction between heme and A(1-40). It was proven that a heme-A(1-40) complex is formed and can stabilize the -helix structure of A(1-40) to inhibit A(1-40) aggregation. The heme-A(1-40) complex possesses peroxidase activity and it may catalyze the decomposition of H(2)O(2), reduce the generation of ROS downstream, and ultimately protect the cells. These results indicated that exogenous heme is able to alleviate the cytotoxicity induced by A(1-40) and Cu(2+). This information may be a foundation to develop a potential strategy to treat AD.
