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.

Complex‐I inhibition and oxidative processes have been implicated in the loss of nigral dopamine neurones in Parkinson's disease and the toxicity of MPTP and its metabolite MPP⁺. Tetrahydrobiopterin, an essential cofactor for tyrosine hydroxylase, may act as an antioxidant in dopaminergic neurones and protects against the toxic consequences of glutathione depletion. Here we studied the effects of manipulating tetrahydrobiopterin levels on MPP⁺toxicity in organotypic, rat ventral mesencephalic slice cultures. In cultures exposed to 30 µmMPP⁺for 2 days, followed by 8 days ‘recovery’ in control medium, we measured dopamine and its metabolites in the tissue and culture medium by HPLC, lactate dehydrogenase release to the culture medium, cellular uptake of propidium iodide and counted the tyrosine hydroxylase‐immunoreactive neurones. Inhibition of tetrahydrobiopterin synthesis by 2,4‐diamino‐6‐hydroxypyrimidine had no significant synergistic effect on MPP⁺toxicity. In contrast, the tetrahydrobiopterin precursorl‐sepiapterin attenuated the MPP⁺‐induced dopamine depletion and loss of tyrosine hydroxylase‐positive cells in a dose‐dependent manner with 40 µm l‐sepiapterin providing maximal protection. Accordingly, increasing intracellular tetrahydrobiopterin levels may protect against oxidative stress by complex‐I inhibition.