New research suggests that two proteins known for their role in the cardiovascular system also play a key role in the development of Alzheimer’s disease.
SRF (serum response factor) and myocardin help to control the rate at which blood flows through the blood vessels. Previously, Berislav Zlokovic and Joseph Miano and colleagues found that these two proteins are much more active in the blood vessels of the brains of people with Alzheimer’s disease, and that this increased activity reduces blood flow in the brain.
Further research by the same group has now revealed that SRF and myocardin turn on a molecule called SREBP2, which, in turn, inhibits LRP-1 – a protein that helps the body to dispose of the toxic protein aggregate amyloid beta. Thus, suggesting that increased activity of SRF and myocardin not only slows blood flow in the brain, but also reduces the body’s ability to remove amyloid beta – the main component of the amyloid plaques that are present in the brains of Alzheimer’s disease patients.
By comparing smooth muscle cells taken from Alzheimer’s disease patients to those obtained from healthy adults, the researchers found that cells from Alzheimer’s patients contained approximately five times more myocardin, four times more SRF, five times more SREBP2, and roughly 60% less LRP-1. Such a dramatic reduction in LRP-1 levels suggests that people with Alzheimer’s disease have less than one-third of the normal capacity to remove amyloid beta.
Further investigations in cells taken from Alzheimer’s patients showed that lowering SRF levels to normal levels lead to significant improvements in the cells capacity for removing amyloid beta. On the other hand, boosting SRF and myocardin levels in healthy cells significantly reduced their capacity for removing beta amyloid. Similar results were also obtained in studies on mice.
Bell RD, Deane R, Chow N, et al. SRF and myocardin regulate LRP-mediated amyloid-bold beta clearance in brain vascular cells. Nature Cell Biology. Published online: 21 December 2008. doi:10.1038/ncb1819
News release: Two cardiovascular proteins pose a double whammy in Alzheimer’s. University of Rochester Medical Center. December 21st 2008.
