SAME и DADS ослабили демиелинацию, вызванную кухонной зоной, посредством модуляции H2S/AMPK/SIRT1/ULK1/beclin1.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
El-Boghdady Noha A, Elsayed Esraa I, Samir Ahmed, Abdelmonem Maha
Аннотация
Оригинал публикации
SAMe and DADS attenuated cuprizone-induced demyelination via modulating H2S/AMPK/SIRT1/ULK1/beclin1 signaling.
Multiple sclerosis (MS) is a chronic demyelinating and inflammatory neurodegenerative disease that impacts more than 2.8 million patients worldwide. Hydrogen sulfide (H2S) impairment and dysregulation are implicated in the pathogenesis of MS. The current study aims to explore the potential protective effects of H2S modulating drugs; diallyl disulfide (DADS) and S-adenosyl-l-Methionine (SAMe) on cuprizone-induced demyelination and to investigate their molecular mechanisms. Male C57BI/6 mice were randomly divided into four groups; control, cuprizone, cuprizone + DADS (100 mg/kg/day, p.o.) and cuprizone + SAMe (20 mg/kg/day, p.o.) groups. Interestingly, treatment with DADS and SAMe successfully enhanced the motor coordination, CBS enzymatic activity and attenuated cuprizone-induced demyelination. They also suppressed neuroinflammation as demonstrated by LFB-stained and H&E-stained corpus callosum. Their neuroprotective effects were further confirmed by the increased levels of the oligodendrocyte markers MBP, Olig2 and CNTF. DADS and SAMe treatments led to restoration of autophagic flux evidenced by the enhanced levels of ULK1, beclin1, ATG5 and LC3-II through upregulation of both AMPK and SIRT1. Additionally, DADS and SAMe suppressed NF-κB and IL-17 levels and increased GSH and TAC, curbing both neuroinflammation and oxidative stress. Furthermore, the levels of fibronectin aggregates were significantly reduced compared to the untreated group. The study also demonstrated that SAMe has superior effects in curbing demyelination, inflammation and oxidative stress and inducing autophagy compared to DADS. The current investigation highlights for the first time that the H2S modulating agents (SAMe and DADS) could provide promising treatment options for cuprizone-induced demyelination via regulating H2S/AMPK/SIRT1/ULK1/beclin1 pathway.