Searching for Reliable Premortem Protein Biomarkers for Prion Diseases

Progress and Challenges to Date

Di Ma; Lingjun Li


Expert Rev Proteomics. 2012;9(3):267-280. 

In This Article

Five-year View

At the current stage, discovery of biomarkers for early detection of prion diseases has been mostly confined to the general profiling of the proteome in easily accessible biological fluids. Now that the important role of glycosylation in neurodegenerative diseases has been revealed, the application of MS-based glycoproteomics holds promise in the identification of new glycoprotein biomarkers. Moreover, new approaches allowing the distinction of a prion disease-related glycosylated form of a potential biomarker from the non-glycosylated form or other isoforms will promote the development of diagnostic assays that detect only the glycosylated form of a protein, thus increasing the specificity and lowering the false-positive rate. Structural elucidation of aberrant glycosylation by MS analysis will also provide new insights into the cellular and molecular pathology of prion diseases and lead to the identification of enzymes involved in neuropathogenesis that can be used as diagnostic markers or treatment targets.

The application of a systems biology approach based on datasets from genomic or proteomic analysis will permit discovery of pathophysiological pathways underlying interconnected patterns from seemingly irrelevant misregulated proteins, and thereby highlight the ones with higher probability of being genuine biomarkers for prion diseases.


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