Метод генных сетей и метаболомный анализ позволили выявить специфические пути изменения профиля аминокислот и ацилкарнитинов в плазме крови при болезни Паркинсона и сосудистом паркинсонизме

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.

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