RICHLAND, Wash. -- In Alzheimer's disease, brain neurons become clogged with tangled proteins. Scientists suspect these tangles arise partly due to malfunctions in a little-known regulatory system within cells. Now, researchers have dramatically increased what they know about this particular regulatory system in mice. Such information will help scientists better understand Alzheimer's and other diseases in humans and could eventually provide new targets for therapies.
In a study released online in the Proceedings of the National Academy of Sciences Early Edition this week, the team at least doubled the number of proteins found to be subject to a type of regulation based on a sugar known as O-GlcNAc (oh-GLIK-nak). The O-GlcNAc system likely adds another layer of control to the proteins that serve as a brain cell's widgets and gears -- control that might be muddled in Alzheimer's brains known to have problems in sugar metabolism.
"We found many novel proteins providing insights into new aspects of cell biology," said analytical biochemist Feng Yang of the Department of Energy's Pacific Northwest National Laboratory and lead author on the study. "We think O-GlcNAc is fine-tuning cellular processes."
In addition to finding hundreds of proteins modified by O-GlcNAc, the team found that almost all the O-GlcNAc proteins were also subject to the most common form of protein regulation, which uses small phosphate molecules to turn proteins on and off. This suggests a larger coordination between the two regulatory systems.
"These results show there's a level of complexity about how biology operates that we've been largely blind to," said PNNL's Richard D. Smith, who leads the proteomics team at PNNL. Proteomics researchers try to understand how a cell functions based on the numbers and types of its proteins at work, which are collectively known as the proteome (PRO-tee-ohm).
"Back during the Human Genome Project, we aske
|Contact: Mary Beckman|
DOE/Pacific Northwest National Laboratory