vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-100vavilov-4414Research ArticleСИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯSYSTEMS COMPUTATIONAL BIOLOGYМетод генных сетей и метаболомный анализ позволили выявить специфические пути изменения профиля аминокислот и ацилкарнитинов в плазме крови при болезни Паркинсона и сосудистом паркинсонизмеGene 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 parkinsonismhttps://orcid.org/0009-0005-1844-7921МакароваА. А.MakarovaA. A.

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Novosibirsk

makarovaaa@bionet.nsc.ruМельниковаП. М.MelnikovaP. M.

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Novosibirsk

https://orcid.org/0000-0002-3338-8529РогачевА. Д.RogachevA. D.

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Novosibirsk

https://orcid.org/0000-0001-9433-8341ДеменковП С.DemenkovP. S.

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Novosibirsk

https://orcid.org/0000-0002-0005-9155ИванисенкоТ. В.IvanisenkoT. V.

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Novosibirsk

ПредтеченскаяЕ. В.PredtechenskayaE. V.

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Novosibirsk

КармановС. Ю.KarmanovS. Y.

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Novosibirsk

https://orcid.org/0000-0002-2577-2184КовальВ. В.KovalV. V.

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Novosibirsk

https://orcid.org/0000-0001-5982-8580ПокровскийА. Г.PokrovskyA. G.

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Novosibirsk

ЛаврикИ. Н.LavrikI. N.

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Novosibirsk

https://orcid.org/0000-0001-6800-8787КолчановН. А.KolchanovN. A.

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Novosibirsk

https://orcid.org/0000-0002-1859-4631ИванисенкоВ. А.IvanisenkoV. A.

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Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationНовосибирский национальный исследовательский государственный университетРоссияNovosibirsk State UniversityRussian FederationНовосибирский национальный исследовательский государственный университет; Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наукРоссияNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университет; Курчатовский геномный центр ИЦиГ СО РАНРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASRussian FederationИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian Federation202426012025288927939Copyright © Макарова А.А., Мельникова П.М., Рогачев А.Д., Деменков П.С., Иванисенко Т.В., Предтеченская Е.В., Карманов С.Ю., Коваль В.В., Покровский А.Г., Лаврик И.Н., Колчанов Н.А., Иванисенко В.А., 20252025Макарова А.А., Мельникова П.М., Рогачев А.Д., Деменков П.С., Иванисенко Т.В., Предтеченская Е.В., Карманов С.Ю., Коваль В.В., Покровский А.Г., Лаврик И.Н., Колчанов Н.А., Иванисенко В.А.Makarova A.A., Melnikova P.M., Rogachev A.D., Demenkov P.S., Ivanisenko T.V., Predtechenskaya E.V., Karmanov S.Y., Koval V.V., Pokrovsky A.G., Lavrik I.N., Kolchanov N.A., Ivanisenko V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4414

Болезнь Паркинсона (БП) и сосудистый паркинсонизм (СП) характеризуются схожими неврологическими синдромами, но различаются патогенезом, морфологией и терапевтическими подходами. Их молекулярно­генетические механизмы многофакторны и задействуют множество биологических процессов. Для комплексного анализа патофизиологии этих заболеваний необходимо применение методов системной биологии и реконструкции генных сетей. В данном исследовании проведен метаболомный скрининг аминокислот и ацилкарнитинов в плазме крови трех групп испытуемых: пациентов с БП, пациентов с СП и контрольной группы. Сравнительный статистический анализ метаболомных профилей групп пациентов по сравнению с контролем определил значимо измененные уровни метаболитов при болезни Паркинсона и при сосудистом паркинсонизме. Для выявления потенциальных механизмов нарушения метаболизма аминокислот и ацилкарнитинов при БП и СП были реконструированы регуляторные генные сети с помощью когнитивной системы ANDSystem. Пути регуляции ферментов метаболизма значимых метаболитов были найдены для трех групп генетических маркеров: специфических для БП, специфических для СП, а также группы общих маркеров двух заболеваний. Сравнительный анализ молекулярно­генетических путей в генных сетях позволил выявить как специфические, так и общие для БП и СП молекулярные механизмы, ассоциированные с изменением метаболомного профиля. Обнаружены регуляторные пути, функция которых потенциально нарушена при этих патологиях. Специфическими для генетических маркеров БП оказались пути регуляции ферментов ALDH2, BCAT1, AL1B1 и UD11, а для генетических маркеров СП – пути регуляции ферментов OCTC, FURIN и S22A6. Регуляторные пути к ферментам BCAT2, ODPB и P4HA1 были связаны с общими для обоих заболеваний генетическими маркерами. Полученные результаты углубляют понимание патологических процессов при БП и СП и могут быть использованы для применения диагностических систем на основе оценки метаболомного профиля аминокислот и ацилкарнитинов в плазме крови пациентов с болезнью Паркинсона и сосудистым паркинсонизмом.

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.

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The authors declare that there are no conflicts of interest present.