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Mass Spectrometry for Neurobiomarker Discovery: The Relevance of Post-Translational Modifications
Rita Azevedo1, Chloé Jacquemin1, Nicolas Villain1,2,3
1CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Université Paris-Saclay, 91191 Gif-sur-Yvette, France.
Cells
|April 23, 2022
Summary
Post-translational modifications (PTMs) in cerebrospinal fluid are key to understanding neurodegenerative diseases. Mass spectrometry advances reveal PTM signatures for new diagnostic biomarkers and therapies.
Area of Science:
- Neuroscience
- Biochemistry
- Proteomics
Background:
- Neurodegenerative diseases are incurable, heterogeneous, and age-dependent, posing significant challenges to modern medicine.
- Understanding their pathogenesis is crucial for developing diagnostic biomarkers and disease-modifying therapies.
- Post-translational modifications (PTMs) are increasingly recognized for their significant role in neurodegeneration.
Purpose of the Study:
- To review PTM-modified proteins implicated in neurodegenerative diseases.
- To highlight recent advancements in mass spectrometry (MS)-based biomarker discovery for these conditions.
- To underscore the potential of PTM signatures for clinical applications.
Main Methods:
- Cerebrospinal fluid (CSF) analysis as an indirect measure of brain changes.
- Mass spectrometry (MS) for characterizing PTMs in complex biological matrices like CSF, brain tissue, and blood.
- Focus on identifying specific pathological PTM-signatures.
Main Results:
- MS has enabled extensive characterization of modified proteins, including phosphorylated tau, truncated alpha-synuclein, APP, and TDP-43.
- Significant progress has been made in analyzing complex samples for PTMs.
- Specific pathological PTM-signatures show great potential for clinical use.
Conclusions:
- PTMs are critical players in the pathogenesis of neurodegenerative diseases.
- MS-based approaches are powerful tools for PTM analysis and biomarker discovery in neurodegeneration.
- Identifying pathological PTM-signatures in CSF and other biofluids offers a promising avenue for improved diagnostics and therapeutics.
