Plasma Metabolome Signature in Patients with Early-stage Parkinson Disease

Balashova, Elena E.; Lokhov, Petr G.; Maslov, Dmitry L.; Trifonova, Oxana P.; Khasanova, D. M.; Zalyalova, Z. A.; Нигматуллина, Р. Р.; Archakov, Alexander I.; Ugrumov, M. V.

doi:10.2174/2213235x05666170221161735

Cited by 24 publications

(23 citation statements)

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“…They found an increase in the levels of polyamine metabolites such as 4-aminobutyraldehyde, N-acetylputrescine and asymmetric dimethylarginine. It is important to emphasize that lysine breakdown activates at early stages, with an increased formation of L-lysine 1,6-lactam or fragments of lysine such as diaminohexanoate [57]. Increased lysine breakdown indicates disturbances in the cadaverine metabolism [57].…”

Section: Polyamine Levels In Pdmentioning

confidence: 99%

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

et al. 2019

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Parkinson's disease (PD) is a systemic neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and stooping posture. When more than 60% of dopaminergic neurons in the substantia nigra of the brain have died, motor symptoms manifest in PD. Currently, oxidative stress (OS) is considered to be one of the leading factors provoking death of dopaminergic neurons in PD. This review is concerned with the role of polyamines in PD, especially focusing on their role in OS induction. Polyamines (putrescine, cadaverine, spermidine and spermine) are involved in many molecular mechanisms, including cell proliferation and differentiation, gene transcription and translation, modulation of the functional activity of ion channels and receptors, and other vital processes. It is worth noting that under physiological conditions polyamines are antioxidants. It has been shown that spermine oxidase (SMOX) is up-regulated in PD, activating polyamine breakdown, which leads to excessive formation of toxic aldehydes (such as acrolein), H 2 O 2 (a strong cytostatic) and ammonia (a toxic substance). Polyamines are also involved in the pathogenetic mechanism of α-synuclein modification resulting in the formation of Lewy bodies. This review provides data on the changes in polyamine levels at later stages of the disease. The review also examines the role of polyamines, as gliotransmitters, in regulating neural function and vice versa. The mechanisms of polyamine "pumping" from neurons to glia can be considered factors of OS regulation in neurons. Prolonged accumulation of polyamines in glia can lead to oxidation of polyamines and therefore potentially to gliosis in PD. The exact mechanisms of this process are, however, not clear. Answering the questions regarding the role of polyamines in gliosis development and pathogenesis of PD is necessary for treating cognitive impairment in patients with PD, which is particularly important.

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Section: Polyamine Levels In Pdmentioning

confidence: 99%

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

et al. 2019

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“…The results of the studies using omics methodologies have been highly variable (Table S1); in most of them the sample size is too small [3][4][5][6][7]10,14], and in many of them the measurements of different metabolites are relative [6][7][8]10,13].…”

Section: Discussionmentioning

confidence: 99%

“…One study did not provide standard deviation (SD) values [16]. Six studies did not measure the absolute concentration of amino acids but the relative quantification of many metabolites in individual samples or different groups of samples [3,[6][7][8]10,13]. In another study, CSF absolute concentrations of amino acids were given, but not those of plasma, and therefore it was excluded from the meta-analysis of plasma amino acid levels [5].…”

Section: Criteria For Eligibility and Exclusion Of Studies From The Mmentioning

confidence: 99%

“…Classical studies addressing CSF and serum/plasma concentrations of amino acids in PD patients have been largely inconclusive and have shown high variability, which may be related with several factors such as sample size, differences in the handling and storage of samples or in the study methodologies, the lack of a control group or adequate matching between PD patients and controls, and differences in antiparkinsonian therapies [1]. In recent years, there has been an increasing interest in the potential of proteomics/metabolomics multi-analyte profiles both in CSF [3][4][5][6] and/or in serum/plasma [3,[5][6][7][8][9][10][11][12][13][14] to discriminate PD patients from controls.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson’s disease: review and meta‐analysis

Jiménez‐Jiménez

Alonso‐Navarro

García‐Martín

et al. 2020

Euro J of Neurology

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Background and purpose: The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of Parkinson's disease (PD). Methods: This is a review of four databases (PubMed, Embase, MED-LINE and Web of Science-Core Collection) from 1966 to 14 March 2020, with identification of references of interest for the topic. The metaanalysis of eligible studies was done using R software package meta, following the PRISMA and MOOSE guidelines. Results: Compared with age-and sex-matched controls, PD patients showed decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan and lysine, and increased serum/plasma proline and homocysteine levels. Conclusion: Despite the limitations of this study due to the important variability of results between different series, our findings suggest the value of CSF or serum/plasma levels of several amino acids in the discrimination of PD patients from healthy subjects, related to the levels of some amino acids. Methods Search strategy A complete literature search was undertaken, without language restrictions, using four databases (PubMed,

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“…The lack of effective metabolite separation is compensated for by using modern mass spectrometers with high mass resolution, which can detect most metabolites at physiological concentrations ( Figure 4 ). The effectiveness of this approach for metabolic profiling has been confirmed in a series of experiments [ 42 , 43 , 47 , 48 , 51 ], and it appears to be a method that can be optimized for metabolomics-based clinical tests. The high efficiency of DIMS was demonstrated in the metabolomic diagnosis of prostate cancer and lung cancer patients, as well as in the diagnosis of impaired glucose tolerance using mass spectrometers equipped with electrospray ionization (ESI) ion sources [ 42 , 47 , 52 ].…”

Section: Pharmacometabolomics Methodologymentioning

confidence: 99%

A Metabolomics Approach to Pharmacotherapy Personalization

Balashova

Maslov

Lokhov

2018

JPM

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The optimization of drug therapy according to the personal characteristics of patients is a perspective direction in modern medicine. One of the possible ways to achieve such personalization is through the application of “omics” technologies, including current, promising metabolomics methods. This review demonstrates that the analysis of pre-dose metabolite biofluid profiles allows clinicians to predict the effectiveness of a selected drug treatment for a given individual. In the review, it is also shown that the monitoring of post-dose metabolite profiles could allow clinicians to evaluate drug efficiency, the reaction of the host to the treatment, and the outcome of the therapy. A comparative description of pharmacotherapy personalization (pharmacogenomics, pharmacoproteomics, and therapeutic drug monitoring) and personalization based on the analysis of metabolite profiles for biofluids (pharmacometabolomics) is also provided.

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Plasma Metabolome Signature in Patients with Early-stage Parkinson Disease

Cited by 24 publications

References 0 publications

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson’s disease: review and meta‐analysis

A Metabolomics Approach to Pharmacotherapy Personalization

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