Alpha-Synuclein post-Translational modifications as potential biomarkers for parkinson disease and other synucleinopathies

Adrien W. Schmid, Bruno Fauvet, Marc Moniatte, Hilal A. Lashuel

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The development of novel therapies against neurodegenerative disorders requires the ability to detect their early, presymptomatic manifestations in order to enable treatment before irreversible cellular damage occurs. Precocious signs indicative of neurodegeneration include characteristic changes in certain protein levels, which can be used as diagnostic biomarkers when they can be detected in fluids such as blood plasma or cerebrospinal fluid. In the case of synucleinopathies, cerebrospinal alpha-synuclein (α-syn) has attracted great interest as a potential biomarker; however, there is ongoing debate regarding the association between cerebrospinal α-syn levels and neurodegeneration in Parkinson disease and synucleinopathies. Post-translational modifications (PTMs) have emerged as important determinants of α-syn's physiological and pathological functions. Several PTMs are enriched within Lewy bodies and exist at higher levels in α-synucleinopathy brains, suggesting that certain modified forms of α-syn might be more relevant biomarkers than the total α-syn levels. However, the quantification of PTMs in bodily fluids poses several challenges. This review describes the limitations of current immunoassay-based α-syn quantification methods and highlights how these limitations can be overcome using novel mass-spectrometrybased assays. In addition, we describe how advances in chemical synthesis, which have enabled the preparation of α-syn proteins that are site-specifically modified at single or multiple residues, can facilitate the development of more accurate assays for detecting and quantifying α-syn PTMs in health and disease.

Original languageEnglish
Pages (from-to)3543-3558
Number of pages16
JournalMolecular and Cellular Proteomics
Volume12
Issue number12
DOIs
Publication statusPublished - 1 Dec 2013
Externally publishedYes

Fingerprint

alpha-Synuclein
Biomarkers
Post Translational Protein Processing
Parkinson Disease
Assays
Cerebrospinal fluid
Fluids
Lewy Bodies
Brain
Proteins
Blood
Immunoassay
Health
Association reactions
Neurodegenerative Diseases
Cerebrospinal Fluid
Plasmas
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

Alpha-Synuclein post-Translational modifications as potential biomarkers for parkinson disease and other synucleinopathies. / Schmid, Adrien W.; Fauvet, Bruno; Moniatte, Marc; Lashuel, Hilal A.

In: Molecular and Cellular Proteomics, Vol. 12, No. 12, 01.12.2013, p. 3543-3558.

Research output: Contribution to journalArticle

Schmid, Adrien W. ; Fauvet, Bruno ; Moniatte, Marc ; Lashuel, Hilal A. / Alpha-Synuclein post-Translational modifications as potential biomarkers for parkinson disease and other synucleinopathies. In: Molecular and Cellular Proteomics. 2013 ; Vol. 12, No. 12. pp. 3543-3558.
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