利用天然化合物增强淀粉样蛋白 beta 的抑制和分解作用:利用光谱学、显微镜和细胞生物学进行研究

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biophysical chemistry Pub Date : 2024-07-10 DOI:10.1016/j.bpc.2024.107291
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引用次数: 0

摘要

淀粉样蛋白和肽在包括阿尔茨海默病(AD)在内的各种神经退行性疾病的病因中起着关键作用。合成设计的小分子/肽/拟肽化合物有望抑制各种淀粉样变性。然而,对从天然提取物中分离出的具有这种潜力的化合物还缺乏探索。在此,我们研究了印度传统药物Lasunadya Ghrita(LG)在AD中的再利用。LG传统上用于治疗肠道失调和精神疾病。研究人员获得了 LG 的各种提取物,对其进行了表征,并分析了其对 Aβ 聚集的抑制作用。生物物理研究表明,LG 的水提取物(LGWE)在抑制 Aβ 肽聚集和 Aβ40/Aβ42 聚集的去颤方面更有效。核磁共振研究表明,LGWE 可与 Aβ40/Aβ42 的中央疏水区和 C 端残基结合,从而调节聚集,减少细胞膜损伤。此外,LGWE 还能挽救神经元 SH-SY5Y 细胞中的 Aβ 毒性,这体现在 ROS 生成、膜渗漏、细胞凋亡和钙失衡的减少上。值得注意的是,LGWE 对神经细胞和小鼠模型无毒性。因此,我们的研究深入探讨了 LGWE 这种具有改善 Aβ 诱导的神经炎症潜力的再利用药物的机理。
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Enhancing amyloid beta inhibition and disintegration by natural compounds: A study utilizing spectroscopy, microscopy and cell biology

Amyloid proteins and peptides play a pivotal role in the etiology of various neurodegenerative diseases, including Alzheimer's disease (AD). Synthetically designed small molecules/ peptides/ peptidomimetics show promise towards inhibition of various kinds of amyloidosis. However, exploration of compounds isolated from natural extracts having such potential is lacking. Herein, we have investigated the repurposing of a traditional Indian medicine Lasunadya Ghrita (LG) in AD. LG is traditionally used to treat gut dysregulation and mental illnesses. Various extracts of LG were obtained, characterized, and analyzed for inhibition of Aβ aggregation. Biophysical studies show that the water extract of LG (LGWE) is more potent in inhibiting Aβ peptide aggregation and defibrillation of Aβ40/Aβ42 aggregates. NMR studies showed that LGWE binds to the central hydrophobic area and C-terminal residues of Aβ40/Aβ42, thereby modulating the aggregation, and reducing cell membrane damage. Additionally, LGWE rescues Aβ toxicity in neuronal SH-SY5Y cells evident from decreases in ROS generation, membrane leakage, cellular apoptosis, and calcium dyshomeostasis. Notably, LGWE is non-toxic to neuronal cells and mouse models. Our study thus delves into the mechanistic insights of a repurposed drug LGWE with the potential to ameliorate Aβ induced neuroinflammation.

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来源期刊
Biophysical chemistry
Biophysical chemistry 生物-生化与分子生物学
CiteScore
6.10
自引率
10.50%
发文量
121
审稿时长
20 days
期刊介绍: Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.
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