Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
Acetylcarnitine in cerebrospinal fluid and blood as a protective factor for neuromyelitis optica spectrum disorders: a mendelian randomization study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
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.
Xie Zhuxiao, Gai Feng, Liu Lei, Guo Yanjun, Jiang Hanqiu, Zhang Weijiao, Wang Jiawei
Аннотация
BACKGROUND: Neuromyelitis Optica Spectrum Disorders (NMOSD) are a group of diseases that can cause vision loss and paralysis. Some patients with refractory NMOSD continue to experience relapses or even disability after existing treatments, so it is crucial to further investigate the targets for precision therapy. The link between cerebrospinal fluid (CSF) and blood metabolites and the pathogenesis of NMOSD remains underexplored.
METHODS: We conducted a two-sample mendelian randomization (MR) study. Instrumental variables related to 338 CSF metabolites and 486 blood metabolites were extracted from genome-wide association (GWAS) data involved European individuals. A series of sensitivity analyses were applied, including the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out method. Finally, we conducted functional enrichment analysis within MetaboAnalyst 5.0.
RESULTS: We identified 20 CSF metabolites and 11 blood metabolites indicated causality with NMOSD. We observed a protective effect of acetylcarnitine within NMOSD, both in CSF (OR = 0.47, P value = 7.088 × 10-6) and blood (OR = 0.02, P value = 0.017). Moreover, functional enrichment analysis identified a set of metabolic pathways potential related to the pathogenesis of NMOSD.
CONCLUSION: This is the first MR analysis to investigate the causality of CSF and blood metabolites in NMOSD. Acetylcarnitine was a protective factor for NMOSD, with a promising prospect for the treatment of refractory NMOSD. Several other key CSF and blood metabolites could also serve as the candidate molecules for exploring mechanisms and potential drug targets.
METHODS: We conducted a two-sample mendelian randomization (MR) study. Instrumental variables related to 338 CSF metabolites and 486 blood metabolites were extracted from genome-wide association (GWAS) data involved European individuals. A series of sensitivity analyses were applied, including the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out method. Finally, we conducted functional enrichment analysis within MetaboAnalyst 5.0.
RESULTS: We identified 20 CSF metabolites and 11 blood metabolites indicated causality with NMOSD. We observed a protective effect of acetylcarnitine within NMOSD, both in CSF (OR = 0.47, P value = 7.088 × 10-6) and blood (OR = 0.02, P value = 0.017). Moreover, functional enrichment analysis identified a set of metabolic pathways potential related to the pathogenesis of NMOSD.
CONCLUSION: This is the first MR analysis to investigate the causality of CSF and blood metabolites in NMOSD. Acetylcarnitine was a protective factor for NMOSD, with a promising prospect for the treatment of refractory NMOSD. Several other key CSF and blood metabolites could also serve as the candidate molecules for exploring mechanisms and potential drug targets.