青蒿素在阿尔茨海默病动物模型中的神经保护作用

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-10-18 DOI:10.2174/0109298673312842241003111836
Susanna Tiratsuyan, Yelena Hambardzumyan, Michael Poghosyan, Margarita Danielyan, Ashkhen Hovhannisyan
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引用次数: 0

摘要

简介:阿尔茨海默病(AD)是老年人最常见的神经退行性疾病:阿尔茨海默病(AD)是老年人最常见的神经退行性疾病,其特征是β-淀粉样蛋白(Aβ)斑块和神经纤维缠结的积累,这些斑块和缠结由高磷酸化tau蛋白聚集而成,而tau蛋白通常有助于稳定神经元中的微管:如今,青蒿素(ART)及其半合成衍生物(ARTs)被视为潜在的神经保护剂。本研究的目标是评估青蒿素的神经保护和抗菌活性,并对青蒿素与 Aβ 肽的亲和性进行硅学研究,寻找青蒿素的潜在靶点。这项研究是指通过电生理学和形态学分析,探讨抗逆转录病毒疗法对聚集性淀粉样蛋白生成肽 Aβ1-42 诱导的 AD 动物模型的影响。具体来说,重点是激活内叶皮层(ENT)的突触电位:结果:电生理学和组织化学研究表明,注射 ART 或其衍生物具有神经保护作用,这种治疗似乎可以防止或减缓脑组织的损伤,促进神经元及其周围环境的恢复。ART的保护作用可能涉及多种机制,包括抗氧化活性、抗炎作用和抑制细胞凋亡。结论:硅学研究显示,ART与淀粉样蛋白生成肽5Aβ17-42、12Aβ9-40和18Aβ9-40有直接、强烈的相互作用。在 CYP2B6 的活性位点上发现了最高的结合亲和力。ART 在利用联合疗法发现新药方面具有巨大潜力。
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Neuroprotective Effect of Artemisinin in an Animal Model of Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disease in older people, characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of aggregated of hyperphosphorylated tau protein, which normally helps stabilize microtubules in neurons.

Method: Nowadays, artemisinin (ART) as well as its semisynthetic derivatives (ARTs) are seen as potential neuroprotectors. The goal of the present study is the assessment of neuroprotective, antibacterial activity of ART, as well as in silico studies of ART affinity to Aβ-peptides and the search of potential targets for ART. The study is referring to explores the impact of ART on an animal model of AD that is induced by the aggregated amyloidogenic peptide Aβ1-42 by electrophysiology and morphology analysis. Specifically, the focus is on the activation of the entorhinal cortex (ENT) as synaptic potentiation.

Result: Electrophysiological and histochemical have demonstrated that therapeutic injection of ART or its derivatives acts as a neuroprotective This treatment appears to prevent or slow down damage to brain tissue, and it promotes the restoration of neurons and their surrounding environment. The protective effects of ART may involve various mechanisms, including antioxidant activity, anti-inflammatory effects, and the inhibition of apoptosis.

Conclusion: in silico studies revealed a direct, strong interaction of ART with the amyloidogenic peptides 5Aβ17-42, 12Aβ9-40, and 18Aβ9-40. in silico screening revealed several protein targets for ART, including cytochrome P-450 2B6 (CYP2B6). The highest binding affinity was found on the active site of CYP2B6. ART has great potential for discovering new drugs using combined therapies.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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