Mass Spectrometry for Neurobiomarker Discovery: The Relevance of Post-Translational Modifications

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Apr 23

PMID 35455959

Authors

Rita Azevedo

Chloe Jacquemin

Nicolas Villain

Francois Fenaille

Foudil Lamari

Francois Becher

Affiliations

Soon will be listed here.

Abstract

Neurodegenerative diseases are incurable, heterogeneous, and age-dependent disorders that challenge modern medicine. A deeper understanding of the pathogenesis underlying neurodegenerative diseases is necessary to solve the unmet need for new diagnostic biomarkers and disease-modifying therapy and reduce these diseases' burden. Specifically, post-translational modifications (PTMs) play a significant role in neurodegeneration. Due to its proximity to the brain parenchyma, cerebrospinal fluid (CSF) has long been used as an indirect way to measure changes in the brain. Mass spectrometry (MS) analysis in neurodegenerative diseases focusing on PTMs and in the context of biomarker discovery has improved and opened venues for analyzing more complex matrices such as brain tissue and blood. Notably, phosphorylated tau protein, truncated α-synuclein, APP and TDP-43, and many other modifications were extensively characterized by MS. Great potential is underlying specific pathological PTM-signatures for clinical application. This review focuses on PTM-modified proteins involved in neurodegenerative diseases and highlights the most important and recent breakthroughs in MS-based biomarker discovery.

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References

Barthelemy N, Li Y, Joseph-Mathurin N, Gordon B, Hassenstab J, Benzinger T . A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease. Nat Med. 2020; 26(3):398-407. PMC: 7309367. DOI: 10.1038/s41591-020-0781-z. View

Mannino M, Hart G . The Beginner's Guide to -GlcNAc: From Nutrient Sensitive Pathway Regulation to Its Impact on the Immune System. Front Immunol. 2022; 13:828648. PMC: 8841346. DOI: 10.3389/fimmu.2022.828648. View

Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg M . alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol. 2002; 4(2):160-4. DOI: 10.1038/ncb748. View

Ramazi S, Zahiri J . Posttranslational modifications in proteins: resources, tools and prediction methods. Database (Oxford). 2021; 2021. PMC: 8040245. DOI: 10.1093/database/baab012. View

Ruffini N, Klingenberg S, Schweiger S, Gerber S . Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. Cells. 2020; 9(12). PMC: 7764447. DOI: 10.3390/cells9122642. View

Hansson O . Biomarkers for neurodegenerative diseases. Nat Med. 2021; 27(6):954-963. DOI: 10.1038/s41591-021-01382-x. View

Heemels M . Neurodegenerative diseases. Nature. 2016; 539(7628):179. DOI: 10.1038/539179a. View

Goyallon A, Cholet S, Chapelle M, Junot C, Fenaille F . Evaluation of a combined glycomics and glycoproteomics approach for studying the major glycoproteins present in biofluids: Application to cerebrospinal fluid. Rapid Commun Mass Spectrom. 2015; 29(6):461-73. DOI: 10.1002/rcm.7125. View

Rauniyar N . Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry. Int J Mol Sci. 2015; 16(12):28566-81. PMC: 4691067. DOI: 10.3390/ijms161226120. View

10.

Barthelemy N, Horie K, Sato C, Bateman R . Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer's disease. J Exp Med. 2020; 217(11). PMC: 7596823. DOI: 10.1084/jem.20200861. View

11.

Huseby C, Hoffman C, Cooper G, Cocuron J, Alonso A, Thomas S . Quantification of Tau Protein Lysine Methylation in Aging and Alzheimer's Disease. J Alzheimers Dis. 2019; 71(3):979-991. PMC: 6844542. DOI: 10.3233/JAD-190604. View

12.

Abeliovich A, Gitler A . Defects in trafficking bridge Parkinson's disease pathology and genetics. Nature. 2016; 539(7628):207-216. DOI: 10.1038/nature20414. View

13.

Yuzwa S, Macauley M, Heinonen J, Shan X, Dennis R, He Y . A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol. 2008; 4(8):483-90. DOI: 10.1038/nchembio.96. View

14.

Barthelemy N, Fenaille F, Hirtz C, Sergeant N, Schraen-Maschke S, Vialaret J . Tau Protein Quantification in Human Cerebrospinal Fluid by Targeted Mass Spectrometry at High Sequence Coverage Provides Insights into Its Primary Structure Heterogeneity. J Proteome Res. 2016; 15(2):667-76. DOI: 10.1021/acs.jproteome.5b01001. View

15.

Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M . CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016; 15(7):673-684. DOI: 10.1016/S1474-4422(16)00070-3. View

16.

Fitzpatrick A, Falcon B, He S, Murzin A, Murshudov G, Garringer H . Cryo-EM structures of tau filaments from Alzheimer's disease. Nature. 2017; 547(7662):185-190. PMC: 5552202. DOI: 10.1038/nature23002. View

17.

Mair W, Muntel J, Tepper K, Tang S, Biernat J, Seeley W . FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease. Anal Chem. 2016; 88(7):3704-14. PMC: 5808556. DOI: 10.1021/acs.analchem.5b04509. View

18.

Paleologou K, Oueslati A, Shakked G, Rospigliosi C, Kim H, Lamberto G . Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci. 2010; 30(9):3184-98. PMC: 2947449. DOI: 10.1523/JNEUROSCI.5922-09.2010. View

19.

Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B . Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol. 1999; 56(6):673-80. DOI: 10.1001/archneur.56.6.673. View

20.

Leutert M, Entwisle S, Villen J . Decoding Post-Translational Modification Crosstalk With Proteomics. Mol Cell Proteomics. 2021; 20:100129. PMC: 8430371. DOI: 10.1016/j.mcpro.2021.100129. View