000199150 001__ 199150
000199150 005__ 20180913062521.0
000199150 0247_ $$2doi$$a10.1074/mcp.R113.032730
000199150 022__ $$a1535-9476
000199150 02470 $$2ISI$$a000329993600011
000199150 037__ $$aARTICLE
000199150 245__ $$aAlpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies
000199150 260__ $$bAmer Soc Biochemistry Molecular Biology Inc$$c2013$$aBethesda
000199150 269__ $$a2013
000199150 300__ $$a16
000199150 336__ $$aReviews
000199150 520__ $$aThe 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-spectrometry-based 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.
000199150 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Prote Core Facil, Stn 19, CH-1015 Lausanne, Switzerland$$aSchmid, Adrien W.
000199150 700__ $$0243218$$g160156$$aFauvet, Bruno
000199150 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Prote Core Facil, Stn 19, CH-1015 Lausanne, Switzerland$$aMoniatte, Marc
000199150 700__ $$0240880$$g167337$$aLashuel, Hilal A.
000199150 773__ $$j12$$tMolecular & Cellular Proteomics$$k12$$q3543-3558
000199150 909C0 $$xU11104$$0252159$$pLMNN
000199150 909CO $$pSV$$preview$$ooai:infoscience.tind.io:199150
000199150 917Z8 $$x148230
000199150 937__ $$aEPFL-REVIEW-199150
000199150 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000199150 980__ $$aREVIEW