Computational disruption of paired helical filaments (PHFs) assembly using Milk Lactalbumin-derived peptides against Alzheimer's disease

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2025-05-22 DOI:10.1016/j.jff.2025.106853

Saeed Pourmand , Sara Zareei , Mohanna Jozi , Shokoufeh Massahi

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引用次数: 0

Abstract

Peptides show great potential in diagnosing and treating Alzheimer's disease (AD), particularly by targeting amyloid-beta plaques and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau proteins. This study focuses on designing peptide inhibitors from bovine milk alpha-lactalbumin to reduce tau aggregation in AD. Using computational techniques, such as docking, molecular dynamics simulations, and mutagenesis, we evaluated the binding and stability of these peptides against the paired helical filament (PHF) core. Our results identified promising inhibitors, with p136 emerging as the most effective. It significantly altered the PHF core's structure, preventing further aggregation by blocking additional subunits. Additionally, p76 displayed strong binding against straight filaments (SFs). These findings highlight the potential of peptides derived from bovine milk alpha-lactalbumin as diagnostic and therapeutic tools for AD, with p136 standing out as a promising candidate for disrupting tau aggregation.

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使用乳乳清蛋白衍生肽对阿尔茨海默病的成对螺旋细丝（phf）组装的计算破坏

多肽在诊断和治疗阿尔茨海默病（AD）方面显示出巨大的潜力，特别是针对淀粉样斑块和由过度磷酸化的tau蛋白形成的神经原纤维缠结（nft）。本研究的重点是设计从牛奶α -乳白蛋白中提取的肽抑制剂，以减少AD中的tau聚集。利用对接、分子动力学模拟和诱变等计算技术，我们评估了这些肽对配对螺旋丝（PHF）核心的结合和稳定性。我们的结果确定了有希望的抑制剂，其中p136是最有效的。它显著改变了PHF核心的结构，通过阻断额外的亚基来阻止进一步的聚集。此外，p76对直丝（SFs）表现出较强的结合。这些发现强调了从牛奶α -乳白蛋白中提取的肽作为AD诊断和治疗工具的潜力，其中p136作为破坏tau聚集的有希望的候选者脱颖而出。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.