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研究神经退行性变的机制:优势与机遇。

Studying the mechanisms of neurodegeneration: advantages and opportunities.

作者信息

Torres Angie K, Mira Rodrigo G, Pinto Cristina, Inestrosa Nibaldo C

机构信息

Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Escuela de Medicina, Universidad de Magallanes, Punta Arenas, Chile.

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

Front Cell Neurosci. 2025 Mar 26;19:1559151. doi: 10.3389/fncel.2025.1559151. eCollection 2025.

Abstract

has been widely used as a model organism in neurodevelopment for several decades due to its simplicity, rapid growth, short life cycle, transparency, and rather simple genetics. It has been useful in modeling neurodegenerative diseases by the heterologous expression of the major proteins that form neurodegenerative-linked aggregates such as amyloid- peptide, tau protein, and -synuclein, among others. Furthermore, chemical treatments as well as the existence of several interference RNA libraries, transgenic worm lines, and the possibility of generating new transgenic strains create a magnificent range of possible tools to study the signaling pathways that could confer protection against protein aggregates or, on the contrary, are playing a detrimental role. In this review, we summarize the different models of neurodegenerative diseases with a focus on Alzheimer's and Parkinson's diseases and how genetic tools could be used to dissect the signaling pathways involved in their pathogenesis mentioning several examples. Finally, we discuss the use of pharmacological agents in models that could help to study these disease-associated signaling pathways and the powerful combinations of experimental designs with genetic tools. This review highlights the advantages of as a valuable intermediary between and mammalian models in the development of potential new therapies.

摘要

几十年来,由于其简单性、生长迅速、生命周期短、透明度高以及遗传学相对简单,它已被广泛用作神经发育的模式生物。通过异源表达形成神经退行性相关聚集体的主要蛋白质,如淀粉样肽、tau蛋白和α-突触核蛋白等,它在模拟神经退行性疾病方面很有用。此外,化学处理以及几个干扰RNA文库、转基因虫系的存在,以及产生新的转基因菌株的可能性,创造了一系列丰富的可能工具,用于研究可能赋予针对蛋白质聚集体的保护作用的信号通路,或者相反,正在发挥有害作用的信号通路。在这篇综述中,我们总结了神经退行性疾病的不同模型,重点是阿尔茨海默病和帕金森病,以及如何使用遗传工具剖析其发病机制中涉及的信号通路,并提及几个例子。最后,我们讨论了在该模型中使用药物制剂,这有助于研究这些与疾病相关的信号通路,以及实验设计与遗传工具的强大组合。这篇综述强调了该模型作为在潜在新疗法开发中连接线虫和哺乳动物模型的有价值中间物的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d378/11979225/c30addc15896/fncel-19-1559151-g001.jpg

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