Review of Metabolomics-Based Biomarker Research for Parkinson’s Disease

Li, Xin; Fan, Xiaoying; Yang, Hongtian; Liu, Yufeng

doi:10.1007/s12035-021-02657-7

Cited by 25 publications

(18 citation statements)

References 120 publications

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“…Biomarkers are also needed for distinguishing different PD types, predicting the course of the disease, or monitoring the effect of disease-modifying therapies [18,19]. Metabolomic approaches allow the analysis of a great number of low-molecular-weight molecules, offering an overview of the molecular complexity of a biological system and the metabolic pathways that can be altered in a pathological state [20,21]. Therefore, metabolomic studies are being carried out to identify new biomarkers in PD and other NDs [22,23], as well as therapeutic targets and metabolic alterations implicated in PD pathogenesis [23].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Alterations in a Drosophila Model of Parkinson’s Disease Based on DJ-1 Deficiency

Solana-Manrique

Sanz

Torregrosa

et al. 2022

Cells

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Parkinson’s disease (PD) is the second-most common neurodegenerative disorder, whose physiopathology is still unclear. Moreover, there is an urgent need to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations are associated with this disease. In this context, the aim of this study is to provide a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that the PD model flies exhibited protein metabolism alterations, a shift fromthe tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could contribute to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.

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Section: Introductionmentioning

confidence: 99%

Metabolic Alterations in a Drosophila Model of Parkinson’s Disease Based on DJ-1 Deficiency

Solana-Manrique

Sanz

Torregrosa

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Biomarkers are also needed for distinguishing different PD types, predicting the course of the disease, or monitoring the effect of disease-modifying therapies [18,19]. Metabolomic technologies allow the analysis of a great amount of low-molecular-weight molecules, offering an overview of the molecular complexity of a biological system and the metabolic pathways that can be altered in a pathological state [20,21]. Therefore, metabolomic studies are being carried out to identify new biomarkers in PD and other NDs [22,23] as well as therapeutic targets and metabolic alterations implicated in PD pathogenesis [23].…”

Section: Introductionmentioning

confidence: 99%

Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency

Solana-Manrique

Sanz

Torregrosa

et al. 2021

Preprint

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder whose physiopathology is still unclear. Besides, it is urgent to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations were associated with this disease. In this context, the aim of this study is to give a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1β gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1β mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that PD model flies exhibit protein metabolism alterations, a shift from tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could be contributing to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.

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“…Abnormalities of the TCA cycle have been linked to PD progression and α-synuclein pathology, while fatty acid metabolism may be associated with α-synuclein aggregation [ 3 ]. Li et al (2022) noted that altered levels of aconitic acid in PD patients begins many years before the development of the disease and are maintained throughout the course of the disease [ 5 ]. In this study, reduced levels of succinic acid were observed in plasma PD patients compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the etiology of PD is still not well understood. Researchers point out that all sorts of interactions between age, environmental, and genetic factors may be associated with the development of PD [ 5 ], as well as gut microbiome dysbiosis, which is involved in the development of the disease through the microbiome-gut-brain axis [ 5 , 6 , 7 ], but they also mention a link between the disease severity and inflammatory bowel disease [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Metabolic Disturbances in Parkinson’s Disease Patients

et al. 2022

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Plasma from patients with Parkinson’s disease (PD) is a valuable source of information indicating altered metabolites associated with the risk or progression of the disease. Neurotoxicity of dopaminergic neurons, which is triggered by aggregation of α-synuclein, is the main pathogenic feature of PD. However, a growing body of scientific reports indicates that metabolic changes may precede and directly contribute to neurodegeneration. Identification and characterization of the abnormal metabolic pattern in patients’ plasma are therefore crucial for the search for potential PD biomarkers. The aims of the present study were (1) to identify metabolic alterations in plasma metabolome in subjects with PD as compared with the controls; (2) to find new potential markers, some correlations among them; (3) to identify metabolic pathways relevant to the pathophysiology of PD. Plasma samples from patients with PD (n = 25) and control group (n = 12) were collected and the gas chromatography-time-of-flight-mass spectrometry GC-TOFMS-based metabolomics approach was used to evaluate the metabolic changes based on the identified 14 metabolites with significantly altered levels using univariate and multivariate statistical analysis. The panel, including 6 metabolites (L-3-methoxytyrosine, aconitic acid, L-methionine, 13-docosenamide, hippuric acid, 9,12-octadecadienoic acid), was identified to discriminate PD from controls with the area under the curve (AUC) of 0.975, with an accuracy of 92%. We also used statistical criteria to identify the significantly altered level of metabolites. The metabolic pathways involved were associated with linoleic acid metabolism, mitochondrial electron transport chain, glycerolipid metabolism, and bile acid biosynthesis. These abnormal metabolic changes in the plasma of patients with PD were mainly related to the amino acid metabolism, TCA cycle metabolism, and mitochondrial function.

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Review of Metabolomics-Based Biomarker Research for Parkinson’s Disease

Cited by 25 publications

References 120 publications

Metabolic Alterations in a Drosophila Model of Parkinson’s Disease Based on DJ-1 Deficiency

Metabolic Alterations in a Drosophila Model of Parkinson’s Disease Based on DJ-1 Deficiency

Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency

Plasma Metabolic Disturbances in Parkinson’s Disease Patients

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