image: Graph displaying the range of biological variation of the platelet proteome overlaid on a colored 2D-gel used to measure platelet protein expression. view more
Credit: Rudolf Oehler, Medical University of Vienna
Searching for Amyloid Interactions
Researchers have undertaken a large-scale investigation into the molecular environment of the amyloid precursor protein (APP), a protein centrally associated with Alzheimer's disease.
A defining hallmark of Alzheimer's is the extracellular accumulation of amyloid plaques in the diseased brain. These plaques arise from the cleavage of APP, which generates short, sticky fragments called amyloid B-peptides. Despite intense research efforts, however, the function of APP remains enigmatic and only a few proteins are known to interact with it.
Gerold Schmitt-Ulms and colleagues employed a technique called 'time-controlled transcardiac perfusion cross-linking" to uncover more APP-interacting proteins. They pumped a chemical through a mouse's body that would permanently cross-link any proteins that were in close proximity. They could then fish out APP from the brain and study what it was linked to.
From their perfusion, Schmitt-Ulms and colleagues confirmed eight previously reported APP interactions and also identified over 30 new, potentially interacting proteins. They also mapped the interactions of two proteins related to APP that are not known to cause disease, to sense which interactions the three related proteins had in common and which were APP-specific; interestingly the majority of the potential binding partners were specific to APP.
This work constitutes the most comprehensive analysis of the APP interactome to date and may finally shed light on the functional roles of APP in the brain. The researchers believe further investigations of these new interactions may reveal an "Achilles' heel" in the biology of APP that can be exploited for diagnosis or therapy.
CORRESPONDING AUTHOR: Gerold Schmitt-Ulms, the Centre for Research in Neurodegenerative Diseases at the University of Toronto, Ontario; Phone: (416) 946-0066, email: g.schmittulms@utoronto.ca
Low Variation in Platelet Protein Expression within the Elderly
The variation in human platelets in the elderly population is not significantly large, report researchers in a study that has strong implications for clinical biomarker research.
The onset or progression of diseases like cancer is accompanied by changes in the expression of specific proteins. These proteins could be used as biomarkers to diagnose patients early or track therapy progression. However, identifying clinical biomarkers requires knowing the extent of natural protein variation in the population, which arises from a combination of factors like age, gender, and genetic background.
Rudolf Oehler and colleagues examined the platelet protein variation in 20 individuals aged 56-100, an age group at higher for many diseases. Interestingly, while their analysis had a 7% variation from technical accuracy, the total variation was only 18%, although a few proteins did show dramatic differences.
Since the variation of protein expression in normal platelets is fairly low, any changes in protein expression associated with disease will likely also be small (i.e. a low expression range in a healthy population means you don't need big changes to perturb the system).
Platelets play a key role in maintaining the health of our blood and since they're easy to extract they may be a valuable source for protein biomarkers. Due to the naturally low variation, though, Oehler and colleagues note that finding these biomarkers requires highly sensitive and accurate equipment.
CORRESPONDING AUTHOR: Rudolf Oehler, The Medical University of Vienna, Austria; Phone: 43-1-40400-6979; E-mail: rudolf.oehler@meduniwien.ac.at
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at www.asbmb.org.
Journal
Molecular & Cellular Proteomics