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评估阿尔茨海默病转基因秀丽隐杆线虫模型中的β-淀粉样蛋白聚集和毒性。

Evaluating amyloid-beta aggregation and toxicity in transgenic Caenorhabditis elegans models of Alzheimer's disease.

作者信息

Arantes Leticia Priscilla, Cordeiro Larissa Marafiga, Soares Félix Alexandre Antunes

机构信息

State University of Minas Gerais, Department of Biomedical Sciences and Health, Passos, MG, Brazil.

Federal University of Santa Maria, Center for Natural and Exact Sciences, Department of Biochemistry and Molecular Biology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Camobi, Santa Maria, RS, Brazil.

出版信息

Methods Cell Biol. 2025;192:189-202. doi: 10.1016/bs.mcb.2024.06.001. Epub 2024 Jul 9.

DOI:10.1016/bs.mcb.2024.06.001
PMID:39863391
Abstract

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, clinically characterized by memory loss, cognitive decline, and behavioral disturbances. Its pathogenesis is not fully comprehended but involves intracellular depositions of amyloid beta peptide (Aβ) and neurofibrillary tangles of hyperphosphorylated tau. Currently, pharmacological interventions solely slow the progression of symptoms. Caenorhabditis elegans (C. elegans) is a simple and valuable organism to study the dynamics of Aβ. It may contribute to advancing our comprehension of AD development and progression, as well as to discovering new treatments. Herein, we describe usual protocols for evaluating Aβ aggregation and toxicity in transgenic C. elegans models of AD (CL2006, CL4176, GMC101, and CL2355 strains) through the visualization and quantification of the peptide with specific fluorescent dyes, in addition to the analysis of particular behaviors (paralysis and chemotaxis associated with learning).

摘要

阿尔茨海默病(AD)是老年人痴呆的主要原因,临床特征为记忆力丧失、认知能力下降和行为障碍。其发病机制尚未完全明了,但涉及β淀粉样肽(Aβ)的细胞内沉积和过度磷酸化tau蛋白的神经原纤维缠结。目前,药物干预只能减缓症状进展。秀丽隐杆线虫(C. elegans)是研究Aβ动态变化的一种简单而有价值的生物。它可能有助于增进我们对AD发生发展的理解,并有助于发现新的治疗方法。在此,我们描述了在AD转基因秀丽隐杆线虫模型(CL2006、CL4176、GMC101和CL2355菌株)中评估Aβ聚集和毒性的常用方案,通过使用特定荧光染料对该肽进行可视化和定量分析,以及分析特定行为(与学习相关的麻痹和趋化性)。

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