The Alzheimer’s field has been in a “back to the basics” mode lately. Much research has focused on beta-amyloid, the toxic protein fragment that accumulates in plaques in the brain. Yet drugs that target beta-amyloid have mostly been disappointing in clinical trials.
To broaden scope and gain new insights into the biology of Alzheimer’s, Emory investigators have been making large-scale efforts to catalog alterations of brain proteins. One recent example: Nick Seyfried and Erik Johnson’s enormous collection of proteomics data, published this spring in Nature Medicine. Another can be seen in the systematic mapping of N-glycosylation, just published in Science Advances by pharmacologist Lian Li and colleagues.
“It is very exciting to see, for the first time, the landscape of protein N-glycosylation changes in Alzheimer’s brain,” Li says. “Our results suggest that the N-glycosylation changes may contribute to brain malfunction in Alzheimer’s patients. We believe that targeting N-glycosylation may provide a new opportunity to help combat this devastating dementia.”
Biochemists Rick Cummings and David Smith have a paper in Journal of Biological Chemistry describing antiviral sugar molecules present in human milk. The first author is postdoctoral fellow Ying Yu.
Cummings and Smith are pioneers in the field of glycomics, studying the sugar molecules that decorate our proteins and coat our cells. They have found that human milk contains specialized glycans (carbohydrate linked to other molecules such as protein or lipid) that bind to influenza virus. This is separate from, and a supplement to, the adaptive immunity of antibodies and vaccines.
â€œThe anti-flu glycans are not induced to our knowledge, but are part of a naturally occurring â€˜liquid innate immune systemâ€™ in human milk,â€ Cummings says. â€œWe’re very excited about this, and the availability of the human milk glycome in printed microarray formats will now allow screening for glycan binding to a wide variety of infant pathogens. This came from a single donor, so as to not complicate the matter yet, but work in progress shows that glycans from other donors have many related but also different glycans.â€
He adds that his lab is finding that the glycans in human milk are different overall in complexity and makeup from those in other mammals.
Smith hypothesizes that the glycans may be functioning as “decoy receptors,â€ interfering with the molecules on the surfaces of human cells that viruses use to gain access.
Posted on November 20, 2012
by Quinn Eastman