| Salek et al. (2008) | Samples of cerebellum, cortex, hippocampus, substantia nigra, and striatum from VMAT2-deficient mice. | Age-matched wild-type mice (n = 24) | 1H-NMR | 17 | The substantia nigra consistently exhibited metabolic changes across all time points, with decreased myo-inositol, creatine/phosphocreatine, taurine, choline, and phosphocholine, and increased glutamate compared with control mice. | NMR-based metabolomics differentiated the five brain regions by metabolic profiles across three ages, revealing that VMAT2 reduction impacts metabolism in unaffected tissues and distinguishing hemizygotes from wild-type mice metabolically. |
| Graham et al. (2018) | Brain and serum were biochemically profiled in a mouse model of synucleinopathy induced by α-synuclein fibril injection. | Age-matched control huMonomers mice (n = 18) | 1H-NMR,DI- LCMS/MS | 20 | Top five identify metabolites: trans-4-hydroxyproline, C14:1, C12:1, PC ae C34:0, and C14:2-OH. | These techniques are effective for studying synucleinopathy in mice, supporting longitudinal studies on brain biochemistry during progression. Biomarkers require validation in humans to assess utility for Parkinson's disease risk identification. A total of 71 brain metabolites and 182 serum metabolites were accurately identified and quantified using 1H-NMR and targeted MS, respectively. |
| Yang et al. (2020a,b) | Rats were randomly assigned to LID (n = 10) and PD (n = 10) groups. Metabolite analysis was performed from the mid-brain, cortex, striatum, hippocampus, cerebellum, and hypothalamus. | Rats with saline intervention performed (n = 8) | 1H-NMR, RT-PCR | 20 | Glutamate, glutamine, aspartate, and myo-inositol were identified as key discriminating metabolites. | Results suggest that metabolic disruption of the synaptic Glu-Gln-GABA cycle may underlie the onset of PD and dyskinesia. |
| Toczylowska et al. (2020) | Patients with PD (based on MDS Clinical Diagnostic Criteria for Parkinson's Disease), venous blood samples were collected after overnight fasting and post-levodopa night dose (10:00 PM to 3:00 AM), with serum stored at −80°C until metabolomics analysis. | Healthy volunteers (n = 21) | 1H-NMR | 19 | Increase: acetate, acetone, 3-hydroxybutyrate, L-lysine, glutamate, tyrosine, and phenylalanine Decrease: testosterone, 1-MAG, and glutamine | The presented in vitro and in vivo metabolic profiling methods could monitor serum and brain biochemical changes in future PD therapeutic studies, particularly for evaluating disease-modifying strategies. |
| Villeneuve et al. (2016) | Experiments were conducted using PINK1 knockout rat strains. Brain tissue analysis. | LEH rats (n = 6) | 1H-NMR, MS | 6 | In the cortex, alanine, aspartate, creatine, and glycerophosphocholine varied over time. Only myo-inositol was lower in PINK1 KO animals. In the striatum, alanine, creatine, lactate, and myo-inositol changed over time. Genotypic differences were found in aspartate, taurine, and creatine levels in PINK1 KO animals, with significant changes at specific time points. | These results are critical, revealing late-stage PD abnormalities, such as elevated proton leak and depressed taurine levels, present in asymptomatic stages. This research may enable targeting early processes for pre-movement diagnosis and interventions to halt PD progression. |
| Kumari et al. (2020b) | Idiopathic PD patient (UKPDBB criteria and H&Y scale), urine sample analysis. | Healthy controls (n = 50) | 1H-NMR | 100 | Increased concentrations of ornithine, isoleucine, and β-hydroxybutyrate were observed in both early and advanced PD groups compared with the HC group. | A distinct metabolic pattern in urine samples reveals impairments in ornithine, branched-chain amino acid, citrate cycle, and aromatic amino acid metabolism in PD patients. Metabolite concentration associations with clinical parameters suggest its potential as a biomarker for distinguishing PD patients and evaluating disease severity. |
| Solana-Manrique et al. (2022) | Drosophila melanogaster DJ-1βex54- PD model. | Drosophila melanogaster y1,w1118 (n = 15) | 1H-NMR | 15 | Several important metabolites have been identified. The most important of which are: glycerophospholipid metabolism, alanine, aspartate, and glutamate; citrate cycle (TCA cycle); phenylalanine, tyrosine and tryptophan biosynthesis; phenylalanine metabolism. | Loss of DJ-1β function causes metabolic alterations in amino acid metabolism, glycolysis, and the TCA cycle in PD model flies, potentially contributing to PD pathophysiology and serving as therapeutic targets. Amino acid disturbances may also serve as biomarkers for PD stages, requiring further validation in other preclinical models. |
| Lu et al. (2018) | Male C57BL/6 mice were injected intraperitoneally (i.p.) 30 mg/kg MPTP-HCl – PD model. Brain tissue analysis. | Male C57BL/6 mice received an equal volume of normal saline (n = 30) | 1H-NMR | 30 | Glutamate, N-acetylaspartate, myo-inositol, and taurine | Results suggest that neuron loss and motor impairment in PD are linked to overactive GGC and altered membrane metabolism, leading to excitotoxicity and mitochondrial dysfunction. Changes in NAA, mI, and Tau may reflect compensatory and pathogenic mechanisms. |
| Meoni et al. (2022) | De novo drug-naïve PD (UK Brain Bank Criteria) patients training cohort; blood samples were collected between 8:00 AM and 9:00 AM. | Healthy controls (CTR) (n = 79) | 1H-NMR | 228 | Looking at the discrimination between the two male groups (dn2 PD and CTR), all the selected metabolites and lipoproteins have a probability between 68.4% and 80.2% to distinguish case (dn2 PD) from the control (CTR) group. A model based on the concentrations of 27 metabolites and 111 lipoproteins was built to assess its performance in discriminating male dn2 PD patients and male CTR subjects. | Serum changes associated with increased oxidative stress in early PD, detectable in metabolites and lipoproteins, suggest accelerated aging in PD, linking oxidative stress to aging, a key risk factor for PD. Further studies are needed to investigate oxidative stress and PD pathogenesis in the CNS, with an identified interaction between gender and metabolism. |
| Kumari et al. (2020a) | PD-model rats serum analysis; patients in various stages of PD serum analysis | (n = 6) and healthy human (n = 50) | 1H-NMR | Rats: 6 Human: 256 | Trimethylamine N-oxide, acetate, citrate, GPC, alanine, glycine, glutamine | This study reveals distinct metabolic profiles in PD serum compared with controls, identifying altered pathways such as amino acid, energy, and lipid metabolism, the gut microbiota system, and the TCA cycle. Metabolomic signatures, including amino acids, lipids, and microbiota-derived metabolites, may serve as diagnostic markers for PD, highlighting the human microbiome as a potential risk factor. |
| Zheng et al. (2016) | Rats with PD treated with bFGF (n = 10) or saline (n = 10); Brain tissue analysis. | Rats without PD, saline was administered (n = unclear) | 1H-NMR | 20 | GABA, glutamate, glutamine, lactate, N-acetylaspartate, creatine, taurine, myo-inositol | bFGF treatment may restore PD-induced metabolic changes to a normal metabolic state in rats. |
