ЛИЗОСФИНГОЛИПИДЫ КРОВИ В ДИАГНОСТИКЕ ЗАБОЛЕВАНИЙ, АССОЦИИРОВАННЫХ С ДИСФУНКЦИЕЙ ЛИЗОСОМ
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Ключевые слова

лизосфинголипиды
ВЭЖХ/МС/МС
лизосомные болезни накопления
болезнь Паркинсона

Как цитировать

Усенко, Т. С., Байдакова , Г. В., Захарова, Е. Ю., & Пчелина, С. Н. (2020). ЛИЗОСФИНГОЛИПИДЫ КРОВИ В ДИАГНОСТИКЕ ЗАБОЛЕВАНИЙ, АССОЦИИРОВАННЫХ С ДИСФУНКЦИЕЙ ЛИЗОСОМ. Российский физиологический журнал им. И. М. Сеченова, 106(8), 952–963. извлечено от https://rusjphysiol.org/index.php/rusjphysiol/article/view/809

Аннотация

Лизосфинголипиды представляют собой N-деацетилированную форму сфинголипидов и рассматриваются как потенциальные маркеры заболеваний, относящихся к лизосомным болезням накопления (ЛБН), таким как болезни Гоше, Фабри, Краббе и болезнь Ниманна — Пика, а также крайне редким ЛБН, таким как GM1 и GM2 ганглиозидозов. На сегодняшний день существует разнообразие методов для оценки уровня лизосфинголипидов в плазме крови. Однако наиболее перспективным является метод жидкостной хроматографии и тандемной масс-спектрометрии (ВЭЖХ/МС/МС), который позволяет проведение одновременной оценки концентрации нескольких лизосфинголипидов, таких как HexSph (смесь GlcSph и GalSph), LysoGb3, LysoGM1, LysoGM2, LysoSM и LysoSM509 в плазме, моче, сухих пятнах крови. Несмотря на то, что оценка лизосфинголипидов в плазме крови является золотым стандартом, метод проведения ВЭЖХ/МС/МС при экстракции метаболитов из сухих пятен крови является быстрым и надежным методом для оценки количественного состава лизосфинголипидов, позволяющим идентифицировать ЛБН такие как болезнь Гоше (HexSph), болезнь Фабри (LysoGb3), недостаточность просапозина (HexSph, LysoGb3), болезнь Ниманна-Пика типа А/В и С (LysoSM и LysoSM509). Диагностика ряда ЛБН с оценкой концентрации лизосфинголипидов в крови методом ВЭЖХ/МС/МС проводится в настоящее время в Медико-генетическом научном центре, Москва. Нами данный метод применен для оценки уровня лизосфинголипидов при болезни Паркинсона, ассоциированной с мутацией в гене лизосомного фермента - глюкоцереброзидазы (GBA-БП). Впервые показано повышение уровня HexSph (галактозилсфингозин - GalSph) и глюкозилсфингозина (GlcSph) в крови у пациентов с GBA-болезни Паркинсона, что позволяет сделать предположение о механизме патогенеза данного заболевания. В настоящем обзоре описаны подходы к диагностике ЛБН с использованием оценки лизосфинголипидов крови, а также обсуждается возможное участие данных метаболитов в стабилизации нейротоксичных форм альфа-синуклеина при болезни Паркинсона.

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