Mass spectrometry-based proteomics and peptidomics for biomarker discovery in neurodegenerative diseases

Abstract

There is an urgent need to search for biomarkers that are indicative of neurodegenerative diseases, as the clinical diagnosis of which remains unsatisfactory. Mass spectrometry (MS) has been playing an important role in studying peptide and protein identities, structures, modifications and interactions that collectively drive their biological functions. MS-based proteomics technology is thus well suited for the biomarker discovery. This article reviews the overall strategies and workflows employed for biomarker discovery and recent applications of MS-based proteomics in neurodegenerative diseases. Special emphasis is placed on the studies of protein post-translational modification pattern changes and differential peptidomics under these pathological conditions.

Keywords: Biomarker; mass spectrometry; neurodegenerative diseases; peptidomics; post-translational modifications; proteomics.

Figure 1

Overview of the workflow of MS-based proteomics/peptidomics for biomarker discovery. Path A illustrates a typical procedure for a proteomic study of post-translational modification (PTM), with an additional step of enriching the proteins with a particular PTM. Path B reveals the workflow of a peptidomics study, in which the peptidome is separated from the samples by ultrafiltration with low molecular weight filtrate preserved for subsequent analyses. After sample preparation steps the peptides are fractionated by HPLC and characterized by MS and MS/MS. The data processing is followed by a validation step, which usually involves immuno-based assays.