Most proteomic quantitative analyses are thus based on isotope labeling, which consists

in the introduction of a mass tag (i.e., heavy or light) to differentiate identical peptides from various samples in MS owing to a mass shift. Isotope labeling can be done at various levels (i.e., cell, protein, peptide) on different reactive groups (i.e., cysteine, lysine containing residues) and allow sample multiplexing. During the past years, IDH phosphorylation several methods were developed including stable isotope metabolic labeling for cultured cells (SILAC), isotope-coded affinity tags (ICAT) or isobaric tagging technologies either using tandem mass tags (TMT) [216] and [217] or isobaric tags for relative and absolute quantification (iTRAQ)

[218] and [219]. In isobaric labeling, the total mass of the tag is kept constant owing to a mass normalizer group, and identical peptides from different samples sharing the same chromatographic properties co-elute in the mass spectrometer. Labeled peptides thus appear at the same mass in an MS scan, but give rise to low mass reporter signature ions upon CID fragmentation in MS/MS mode (i.e., between 126 and 131 m/z for TMT-6). This robust approach has been one of the most beneficial for the analysis of body fluids and tissues as it allows the simultaneous peptide identification and quantification of up to 10 samples in a single MS/MS experiment. The comprehensive Small molecule library analysis of specific PTMs known to be important for PD, such as oxidation, nitration, phosphorylation, glycosylation or ubiquitination ADAMTS5 can also be addressed. Generally, proteomes of interest are specifically enriched before being analyzed by MS quantitative techniques. Alternatively, peptides with defined PTMS can be targeted based on their MS

fragmentation characteristics (i.e., neutral loss, multiple reaction monitoring MS modes). Selected Reaction Monitoring (SRM) allows the targeting and measurement of selected signature peptides from molecules of interest (reviewed in [220]). Given its unique potential to quantify reliably low abundant analytes in complex mixtures, SRM may represent an alternative to ELISA for clinical validation measurements which are dependent on antibody availability. Importantly, absolute quantification can be obtained through AQUA method, with the spiking of a known quantity of an isotope- labeled peptide as an internal standard, followed by SRM MS analysis [221]. To date, the clinical management of PD patients is still hampered by the lack of reliable diagnostic and therapeutic biomarkers which might pave the way for the development of better options and PD treatment and prevention. Traditional candidate-based studies have assessed the potential of specific targets typically associated to PD pathophysiology as biomarkers of PD, for example the CSF level of α-SYN.