Biomarker Research in Parkinson’s Disease Using Metabolite Profiling

Abstract

Biomarker research in Parkinson’s disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifactorial disease, which requires a more precise diagnosis and personalized medication to obtain optimal outcome. In recent years, advanced metabolite profiling of body fluids like serum/plasma, CSF or urine, known as “metabolomics”, has become a powerful and promising tool to identify novel biomarkers or “metabolic fingerprints” characteristic for PD at various stages of disease. In this review, we discuss metabolite profiling in clinical and experimental PD. We briefly review the use of different analytical platforms and methodologies and discuss the obtained results, the involved metabolic pathways, the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD.

A metabolic profile of polyamines in parkinson disease: A promising biomarker

“…16,[36][37][38] DiAcSpd levels clearly correlated with both H&Y and UPDRS-III under age-or medication-normalized conditions, and significantly correlated with FA (an index of white matter integrity alterations), in diffuse white matter, similar to our previous report. Notably, even using a multivariate model, DiAcSpd remained significantly correlated with disease severity.…”

“…However, surrogate biomarkers reflecting age-related pathogeneses have not been established. 16,[36][37][38] DiAcSpd levels clearly correlated with both H&Y and UPDRS-III under age-or medication-normalized conditions, and significantly correlated with FA (an index of white matter integrity alterations), in diffuse white matter, similar to our previous report. 34,39 Likewise, higher diagnostic power of DiAcSpd levels was confirmed.…”

Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson’s Disease

“…Despite extensive preclinical studies in PD animal models, there is still a lack of effective neuroprotective drugs for PD available [25,26]. Interestingly, the P13K-AKT-FoxO signaling pathway has been suggested to be implicated in the treatment of PD [27].…”

Integrated use of LC/MS/MS and LC/Q-TOF/MS targeted metabolomics with automated label-free microscopy for quantification of purine metabolites in cultured mammalian cells

“…UPLC/MS/MS tandem quadrupole analyses of adenosine (4), inosine (5), and uric acid (6) were conducted on a Waters Acquity TQD LC/MS/MS platform using 0.1% formic acid in H 2 O and 100% methanol as solvents and a reversed-phase column (Acquity® UPLC HSS T3 column, 100 x 2.1 mm, 1.8 µm internal diameter). A linear gradient was used to separate the analytes: 1% to 25% methanol (0 to 4 minutes), 25% to 98% methanol (4 to 5 minutes), 98% methanol (5 to 7 minutes), 98% to 1% methanol (7 to 7.01 minutes), and re-equilibration of the column with 1% methanol (7.01 to 10 minutes) at a flow rate of 0.…”

“…The detection of catecholamines in patient samples has limited utility for assessment of PD, in part because loss of dopamine is only reliably detected in patients who have not received drug treatment (i.e. drug-naïve patients) or who have discontinued L-DOPA therapy [5]. Recently, nontargeted metabolomics studies using ultra-high-performance liquid chromatographyquadrupole-time-of-flight high-resolution mass spectrometry (UPLC/QTOF/HRMS) analysis of patient samples has illuminated several classes of metabolites that are correlated with PD progression.…”