Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism
Parkinson’s disease (PD) and vascular parkinsonism (VP) are characterized by similar neurological syndromes but differ in pathogenesis, morphology, and therapeutic approaches. The molecular genetic mechanisms of these pathologies are multifactorial and involve multiple biological processes. To compr...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2025-01-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/4414 |
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| author | A. A. Makarova P. M. Melnikova A. D. Rogachev P. S. Demenkov T. V. Ivanisenko E. V. Predtechenskaya S. Y. Karmanov V. V. Koval A. G. Pokrovsky I. N. Lavrik N. A. Kolchanov V. A. Ivanisenko |
| author_facet | A. A. Makarova P. M. Melnikova A. D. Rogachev P. S. Demenkov T. V. Ivanisenko E. V. Predtechenskaya S. Y. Karmanov V. V. Koval A. G. Pokrovsky I. N. Lavrik N. A. Kolchanov V. A. Ivanisenko |
| author_sort | A. A. Makarova |
| collection | DOAJ |
| description | Parkinson’s disease (PD) and vascular parkinsonism (VP) are characterized by similar neurological syndromes but differ in pathogenesis, morphology, and therapeutic approaches. The molecular genetic mechanisms of these pathologies are multifactorial and involve multiple biological processes. To comprehensively analyze the pathophysiology of PD and VP, the methods of systems biology and gene network reconstruction are essential. In the current study, we performed metabolomic screening of amino acids and acylcarnitines in blood plasma of three groups of subjects: PD patients, VP patients and the control group. Comparative statistical analysis of the metabolic profiles identified significantly altered metabolites in the PD and the VP group. To identify potential mechanisms of amino acid and acylcarnitine metabolism disorders in PD and VP, regulatory gene networks were reconstructed using ANDSystem, a cognitive system. Regulatory pathways to the enzymes converting significant metabolites were found from PDspecific genetic markers, VPspecific genetic markers, and the group of genetic markers common to the two diseases. Comparative analysis of molecular genetic pathways in gene networks allowed us to identify both specific and nonspecific molecular mechanisms associated with changes in the metabolomic profile in PD and VP. Regulatory pathways with potentially impaired function in these pathologies were discovered. The regulatory pathways to the enzymes ALDH2, BCAT1, AL1B1, and UD11 were found to be specific for PD, while the pathways regulating OCTC, FURIN, and S22A6 were specific for VP. The pathways regulating BCAT2, ODPB and P4HA1 were associated with genetic markers common to both diseases. The results obtained deepen the understanding of pathological processes in PD and VP and can be used for application of diagnostic systems based on the evaluation of the amino acids and acylcarnitines profile in blood plasma of patients with PD and VP. |
| format | Article |
| id | doaj-art-4ca7d1a2008e47f5bac75f4a435244df |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-4ca7d1a2008e47f5bac75f4a435244df2025-02-01T09:58:14ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592025-01-0128892793910.18699/vjgb-24-1001527Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonismA. A. Makarova0P. M. Melnikova1A. D. Rogachev2P. S. Demenkov3T. V. Ivanisenko4E. V. Predtechenskaya5S. Y. Karmanov6V. V. Koval7A. G. Pokrovsky8I. N. Lavrik9N. A. Kolchanov10V. A. Ivanisenko11Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityNovosibirsk State UniversityNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASNovosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASParkinson’s disease (PD) and vascular parkinsonism (VP) are characterized by similar neurological syndromes but differ in pathogenesis, morphology, and therapeutic approaches. The molecular genetic mechanisms of these pathologies are multifactorial and involve multiple biological processes. To comprehensively analyze the pathophysiology of PD and VP, the methods of systems biology and gene network reconstruction are essential. In the current study, we performed metabolomic screening of amino acids and acylcarnitines in blood plasma of three groups of subjects: PD patients, VP patients and the control group. Comparative statistical analysis of the metabolic profiles identified significantly altered metabolites in the PD and the VP group. To identify potential mechanisms of amino acid and acylcarnitine metabolism disorders in PD and VP, regulatory gene networks were reconstructed using ANDSystem, a cognitive system. Regulatory pathways to the enzymes converting significant metabolites were found from PDspecific genetic markers, VPspecific genetic markers, and the group of genetic markers common to the two diseases. Comparative analysis of molecular genetic pathways in gene networks allowed us to identify both specific and nonspecific molecular mechanisms associated with changes in the metabolomic profile in PD and VP. Regulatory pathways with potentially impaired function in these pathologies were discovered. The regulatory pathways to the enzymes ALDH2, BCAT1, AL1B1, and UD11 were found to be specific for PD, while the pathways regulating OCTC, FURIN, and S22A6 were specific for VP. The pathways regulating BCAT2, ODPB and P4HA1 were associated with genetic markers common to both diseases. The results obtained deepen the understanding of pathological processes in PD and VP and can be used for application of diagnostic systems based on the evaluation of the amino acids and acylcarnitines profile in blood plasma of patients with PD and VP.https://vavilov.elpub.ru/jour/article/view/4414metabolomicsamino acidsacylcarnitinesgene networksgenetic markersparkinson’s diseasevascular parkinsonismneurodegenerationdry plasma stainsbiomarker |
| spellingShingle | A. A. Makarova P. M. Melnikova A. D. Rogachev P. S. Demenkov T. V. Ivanisenko E. V. Predtechenskaya S. Y. Karmanov V. V. Koval A. G. Pokrovsky I. N. Lavrik N. A. Kolchanov V. A. Ivanisenko Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism Вавиловский журнал генетики и селекции metabolomics amino acids acylcarnitines gene networks genetic markers parkinson’s disease vascular parkinsonism neurodegeneration dry plasma stains biomarker |
| title | Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism |
| title_full | Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism |
| title_fullStr | Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism |
| title_full_unstemmed | Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism |
| title_short | Gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with Parkinson’s disease and vascular parkinsonism |
| title_sort | gene networks and metabolomic screening analysis revealed specific pathways of amino acid and acylcarnitine profile alterations in blood plasma of patients with parkinson s disease and vascular parkinsonism |
| topic | metabolomics amino acids acylcarnitines gene networks genetic markers parkinson’s disease vascular parkinsonism neurodegeneration dry plasma stains biomarker |
| url | https://vavilov.elpub.ru/jour/article/view/4414 |
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