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蜂毒肽类似物 Octovespin 可预防阿尔茨海默病小鼠模型中由淀粉样β诱导的认知障碍。

Octovespin, a peptide bioinspired by wasp venom, prevents cognitive deficits induced by amyloid-β in Alzheimer's disease mouse model.

机构信息

Neuropharma Lab, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, Brazil.

Neuropharma Lab, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília, Brazil.

出版信息

Neuropeptides. 2022 Jun;93:102233. doi: 10.1016/j.npep.2022.102233. Epub 2022 Mar 11.

DOI:10.1016/j.npep.2022.102233
PMID:35305448
Abstract

Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most common type is Alzheimer's disease (AD). Since the current AD treatment is incipient and limited, it is essential to develop new drugs to prevent AD. Considering that evolutionary pressure selected animal venom compounds that are very specific for a unique target, those can be a potential drug against AD. Octovespin was modified from occidentalin-1202, which is a peptide isolated from Polybia occidentalis wasp venom. In this context, this study evaluated the effect of treatment with octovespin against Amyloid-β (Aβ)-induced toxicity, which is postulated to be one of the main causes of AD, in both in vitro and in vivo tests. In vitro, octovespin was able to prevent Aβ aggregation in a ThT assay. In vivo, octovespin (0.15 nmol/animal) reverses memory impairment that is due to Aβ toxicity, in the Morris Water Maze and Novel Object Recognition Test. Our results suggested that octovespin is a potential drug for the treatment of AD, due to its ability to avoid Aβ aggregation in vitro and to prevent Aβ -induced memory deficit in mice.

摘要

全世界约有 4680 万人被诊断患有痴呆症,其中最常见的类型是阿尔茨海默病(AD)。由于目前的 AD 治疗方法还处于初期且有限,因此开发新的药物来预防 AD 至关重要。考虑到进化压力选择了针对独特靶标的非常特异的动物毒液化合物,这些化合物可能是对抗 AD 的潜在药物。Octovespin 是从 Polybia occidentalis 黄蜂毒液中分离出的肽 occidentalin-1202 修饰而来的。在这种情况下,本研究评估了 octovespin 治疗淀粉样蛋白-β(Aβ)诱导的毒性的效果,该毒性被认为是 AD 的主要原因之一,在体外和体内测试中都进行了评估。在体外,Octovespin 能够在 ThT 测定中阻止 Aβ聚集。在体内,Octovespin(0.15 nmol/动物)逆转了由于 Aβ毒性引起的记忆障碍,这是在 Morris 水迷宫和新物体识别测试中观察到的。我们的结果表明,由于其在体外避免 Aβ聚集的能力以及预防 Aβ诱导的小鼠记忆缺陷的能力,Octovespin 是一种治疗 AD 的潜在药物。

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