Alternatively, a large number of biochemical compounds (i.e., catecholamines, neuropeptides, amino acids, enzymes, IgGs, oxidative stress proteins) including PD-related proteins (i.e., α-SYN, DJ-1) were typically measured in CSF, blood or urine [160] and [161] (Table 3). As a major component of LB, α-SYN was one of the most attractive molecules to investigate.

In plasma, levels of oligomeric [162] and phosphorylated [163] α-SYN were found increased in PD patients versus controls whereas in CSF, total α-SYN levels [164] and [165] were found repeatedly decreased, although the increased oligomers/total-α-SYN ratio found in PD might be more valuable [166]. However, conflicting results, significant overlap of values between groups, insufficient Epigenetics Compound Library screening sensitivity and specificity preclude the use of α-SYN as a valid marker at the moment [167]. Several studies demonstrated inconsistent results regarding DJ-1 levels in the CSF, whose combination with other molecule measurements might be more helpful for PD diagnosis [168]. Recently, a quantitative Luminex assay demonstrated that the combination of α-SYN and DJ-1 measurements with five other molecules (total tau, phospho-tau, amyloid β1–42, Flt3 ligand and fractalkine) in the CSF could not only help in PD diagnosis and differential

diagnosis but was also correlated with disease progression

and severity [169]. Given the obvious role Venetoclax of oxidative stress in PD pathogenesis, oxidative markers were investigated. For instance, urinary levels of 8-hydroxydeoxyguanosine were shown to be more elevated in PD versus controls and able to evaluate disease progression [170]. Reduced levels of urate, a strong antioxidant, were found in serum, CSF and in the SN of PD patients, which correlate with DA neurodegeneration, advanced PD symptoms and higher risk for developing PD [171], [172] and [173]. While promising for some of them, none of the above biomarkers – taken individually or in combination – has reached a sufficient level of accuracy and reliability allowing their clinical use [174]. The recent emergence of new “candidate-free” Ponatinib manufacturer unbiased disciplines such as proteomics but also genomics and GWAS, transcriptomics, or metabolomics has boost the exploration of new avenues to decipher molecular pathways at the basis of PD pathogenesis and biomarkers for PD diagnosis. Proteomics is a particularly prominent “omic” discipline which systematically studies the protein complement of cells or tissue at a given time [186]. Around 20,000 human genes produce about 150,000 transcripts and more than 1,000,000 proteins as a results of alternative splice variants, RNA editing or PTMs.