New pathogenic insights from large animal models of neurodegenerative diseases
作者机构：Guangdong Key Laboratory of Non-human Primate ResearchGuangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhou 510632China
出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)
年 卷 期：2022年第13卷第10期
页 面：707-720页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：The National Natural Science Foundation of China(81830032,32070534,31872779,82071421) Key Field Research and Development Program of Guangdong province(2018B030337001) Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006) Guangzhou Key Research Program on Brain Science(202007030008) The National Key Research and Development Program of China Stem Cell and Translational Research(2017YFA0105102).
主 题：large animal models neurodegenerative diseases CRISPR/Cas9
摘 要：Animal models are essential for investigating the pathogenesis and developing the treatment of human diseases.Identification of genetic mutations responsible for neurodegenerative diseases has enabled the creation of a large number of small animal models that mimic genetic defects found in the affected individuals.Of the current animal models,rodents with genetic modifications are the most commonly used animal models and provided important insights into pathogenesis.However,most of genetically modified rodent models lack overt neurodegeneration,imposing challenges and obstacles in utilizing them to rigorously test the therapeutic effects on neurodegeneration.Recent studies that used CRISPR/Cas9-targeted large animal(pigs and monkeys)have uncovered important pathological events that resemble neurodegeneration in the patient’s brain but could not be produced in small animal models.Here we highlight the unique nature of large animals to model neurodegenerative diseases as well as the limitations and challenges in establishing large animal models of neurodegenerative diseases,with focus on Huntington disease,Amyotrophic lateral sclerosis,and Parkinson diseases.We also discuss how to use the important pathogenic insights from large animal models to make rodent models more capable of recapitulating important pathological features of neurodegenerative diseases.
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