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利用昆虫模型对阿尔茨海默病、帕金森病和亨廷顿病的特定蛋白直系同源物进行 SNP 预测的计算生物学研究。

In silico SNP prediction of selected protein orthologues in insect models for Alzheimer's, Parkinson's, and Huntington's diseases.

机构信息

Entomology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.

Bioinformatics Group, Center for Informatics Sciences (CIS), School of Information Technology and Computer Science (ITCS) , Nile University, Giza, Egypt.

出版信息

Sci Rep. 2023 Nov 3;13(1):18986. doi: 10.1038/s41598-023-46250-5.

Abstract

Alzheimer's, Parkinson's, and Huntington's are the most common neurodegenerative diseases that are incurable and affect the elderly population. Discovery of effective treatments for these diseases is often difficult, expensive, and serendipitous. Previous comparative studies on different model organisms have revealed that most animals share similar cellular and molecular characteristics. The meta-SNP tool includes four different integrated tools (SIFT, PANTHER, SNAP, and PhD-SNP) was used to identify non synonymous single nucleotide polymorphism (nsSNPs). Prediction of nsSNPs was conducted on three representative proteins for Alzheimer's, Parkinson's, and Huntington's diseases; APPl in Drosophila melanogaster, LRRK1 in Aedes aegypti, and VCPl in Tribolium castaneum. With the possibility of using insect models to investigate neurodegenerative diseases. We conclude from the protein comparative analysis between different insect models and nsSNP analyses that D. melanogaster is the best model for Alzheimer's representing five nsSNPs of the 21 suggested mutations in the APPl protein. Aedes aegypti is the best model for Parkinson's representing three nsSNPs in the LRRK1 protein. Tribolium castaneum is the best model for Huntington's disease representing 13 SNPs of 37 suggested mutations in the VCPl protein. This study aimed to improve human neural health by identifying the best insect to model Alzheimer's, Parkinson's, and Huntington's.

摘要

阿尔茨海默病、帕金森病和亨廷顿病是最常见的神经退行性疾病,无法治愈,影响老年人群体。这些疾病的有效治疗方法的发现往往具有难度大、成本高和偶然性等特点。之前对不同模式生物的比较研究表明,大多数动物具有相似的细胞和分子特征。Meta-SNP 工具包含四个不同的集成工具(SIFT、PANTHER、SNAP 和 PhD-SNP),用于识别非同义单核苷酸多态性(nsSNPs)。对阿尔茨海默病、帕金森病和亨廷顿病的三种代表性蛋白进行了 nsSNP 预测;在果蝇 D. melanogaster 中进行 APP1,在埃及伊蚊 Aedes aegypti 中进行 LRRK1,在赤拟谷盗 Tribolium castaneum 中进行 VCP1。由于有可能使用昆虫模型来研究神经退行性疾病。我们从不同昆虫模型之间的蛋白质比较分析和 nsSNP 分析中得出结论,D. melanogaster 是研究阿尔茨海默病的最佳模型,代表了 APP1 蛋白中 21 个建议突变中的 5 个 nsSNP。Aedes aegypti 是研究帕金森病的最佳模型,代表了 LRRK1 蛋白中的 3 个 nsSNP。Tribolium castaneum 是研究亨廷顿病的最佳模型,代表了 VCP1 蛋白中 37 个建议突变中的 13 个 SNP。本研究旨在通过鉴定最佳的昆虫模型来改善人类神经健康,以研究阿尔茨海默病、帕金森病和亨廷顿病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab4f/10624829/1bdb1ebff91a/41598_2023_46250_Fig1_HTML.jpg

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