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西地那非的复活:对亨廷顿病也有影响?

Resurrection of sildenafil: potential for Huntington's Disease, too?

机构信息

Department of Neurology, Huntington Center North Rhine-Westphalia, Ruhr-University Bochum, St. Josef-Hospital Bochum, Gudrunstraße 56, 44791, Bochum, Germany.

出版信息

J Neurol. 2022 Sep;269(9):5144-5150. doi: 10.1007/s00415-022-11196-7. Epub 2022 May 28.

DOI:10.1007/s00415-022-11196-7
PMID:35633374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9363275/
Abstract

The phosphodiesterase-5 inhibitor sildenafil was postulated to reduce the risk for Alzheimer's Disease. Since preclinical data revealed beneficial effects in Huntington's Disease (HD), we now for the first time investigated effects of sildenafil in HD patients using the database ENROLL-HD. We demonstrate beneficial effects on motoric, functional and cognitive capacities in cross-sectional data. Those effects were not explained by underlying fundamental molecular genetic or demographic data. It remains unsolved, if effects are due to behavioral differences or due to direct dose-dependent neurobiological modulations.

摘要

磷酸二酯酶-5 抑制剂西地那非被认为可以降低阿尔茨海默病的风险。由于临床前数据显示其在亨廷顿病(HD)中有有益作用,我们现在首次使用 ENROLL-HD 数据库研究了西地那非在 HD 患者中的作用。我们在横断面数据中证明了对运动、功能和认知能力的有益影响。这些影响不能用潜在的基本分子遗传或人口统计学数据来解释。其作用是由于行为差异还是由于直接的剂量依赖性神经生物学调节仍未解决。

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本文引用的文献

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Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.基于表型的计算网络医学发现结合保险记录数据挖掘,鉴定西地那非是治疗阿尔茨海默病的候选药物。
Nat Aging. 2021 Dec;1(12):1175-1188. doi: 10.1038/s43587-021-00138-z. Epub 2021 Dec 6.
2
Innovative Therapeutic Approaches for Huntington's Disease: From Nucleic Acids to GPCR-Targeting Small Molecules.亨廷顿舞蹈症的创新治疗方法:从核酸到靶向GPCR的小分子
Front Cell Neurosci. 2021 Nov 26;15:785703. doi: 10.3389/fncel.2021.785703. eCollection 2021.
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Data from ENROLL-HD: Is the prevalence of juvenile and pediatric Huntington's disease overestimated?ENROLL-HD 数据:青少年和儿童亨廷顿病的患病率是否被高估了?
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Longitudinal Evaluation of the Effect of Tricyclic Antidepressants and Neuroleptics on the Course of Huntington's Disease-Data from a Real World Cohort.三环类抗抑郁药和抗精神病药对亨廷顿病病程影响的纵向评估——来自真实世界队列的数据
Brain Sci. 2021 Mar 25;11(4):413. doi: 10.3390/brainsci11040413.
5
Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats.西地那非通过调节血管内皮生长因子和血管细胞黏附分子-1改善大鼠阿尔茨海默病。
Hum Exp Toxicol. 2021 Apr;40(4):596-607. doi: 10.1177/0960327120960775. Epub 2020 Sep 22.
6
Sexual dysfunction in Huntington's Disease: what do we really know?亨廷顿病中的性功能障碍:我们究竟了解多少?
Neurol Neurochir Pol. 2020;54(4):291-293. doi: 10.5603/PJNNS.2020.0034.
7
Phosphodiesterase Inhibitors for Alzheimer's Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale.用于阿尔茨海默病的磷酸二酯酶抑制剂:基于机制原理的临床试验与流行病学系统评价
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Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.磷酸二酯酶抑制剂对神经退行性变的治疗潜力:药物化学家的视角。
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