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输注年轻血液的血浆能对抗阿尔茨海默病吗?

Young Blood Plasma Administration to Fight Alzheimer's Disease?

作者信息

Aicardi Giorgio

机构信息

1 Department for Life Quality Studies, University of Bologna , Bologna, Italy .

2 Interdepartmental Center "Luigi Galvani" for the Integrated Study of Biophysics, Bioinformatics and Biocomplexity, University of Bologna , Bologna, Italy .

出版信息

Rejuvenation Res. 2018 Apr;21(2):178-181. doi: 10.1089/rej.2017.1940. Epub 2017 Apr 6.

Abstract

Despite decades of intensive research, no drugs can cure or even stabilize Alzheimer's disease (AD). Current pharmacological treatments only partially mask the symptoms while the disease progresses within the brain. Finding a preventive measure or a cure for people with AD is indeed a worldwide urgent priority. A recent interesting study by T. Wyss-Coray's research group provides the first evidence that exposure to young blood or plasma can reverse some AD-related molecular and behavioral alterations. Heterochronic parabiosis (shared blood circulation) of AD transgenic mice with young healthy mice did not reduce amyloidosis and microglial activation in AD mice, but reversed the loss of synaptophysin and calbindin (critical synaptic proteins, indicators of cognitive decline in AD) in the dentate gyrus, and the abnormal expression, in the hippocampus, of many genes involved in key neuronal signaling pathways. Moreover, repeated intravenous administration of plasma from young healthy mice to AD mice reversed the excessive phosphorylation of hippocampal extracellular signal-regulated kinase (ERK), and improved spatial working memory and associative memory. Although observations in mouse models of AD might not necessarily extrapolate to humans, this preclinical study provides the first demonstration that young plasma has potential therapeutic properties, by ameliorating aspects of the disease that are present in AD patients. Clinical trials are already under way. If young plasma transfusion will be effective in AD patients, it will be important to identify the key factors responsible for the positive effects, as they might lead to the development of molecule interventions with a better efficacy/risk profile.

摘要

尽管经过了数十年的深入研究,但仍没有药物能够治愈甚至稳定阿尔茨海默病(AD)。目前的药物治疗只能部分掩盖症状,而疾病仍在大脑中继续发展。找到针对AD患者的预防措施或治愈方法确实是全球紧迫的优先事项。T. Wyss-Coray研究小组最近进行的一项有趣研究首次证明,接触年轻血液或血浆可以逆转一些与AD相关的分子和行为改变。将AD转基因小鼠与年轻健康小鼠进行异时联体共生(共享血液循环),并没有减少AD小鼠的淀粉样变性和小胶质细胞激活,但逆转了齿状回中突触素和钙结合蛋白(关键的突触蛋白,是AD认知衰退的指标)的丢失,以及海马体中许多参与关键神经元信号通路的基因的异常表达。此外,将年轻健康小鼠的血浆反复静脉注射给AD小鼠,可逆转海马体细胞外信号调节激酶(ERK)的过度磷酸化,并改善空间工作记忆和联想记忆。尽管在AD小鼠模型中的观察结果不一定能外推至人类,但这项临床前研究首次证明,年轻血浆具有潜在的治疗特性,可改善AD患者身上存在的疾病症状。临床试验已经在进行中。如果年轻血浆输注对AD患者有效,那么识别产生积极效果的关键因素就很重要,因为它们可能会促成具有更好疗效/风险比的分子干预措施的开发。

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