In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models ...In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models to mimic the genetic defects.Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics.However,most genetically modified rodent models lack overt pathological features,imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms.Recent studies using large animals,including pigs and non-human primates,have uncovered important events that resemble neurodegeneration in patients’brains but could not be produced in small animals.Here we describe common features as well as discrepancies among these models,highlighting new insights from these models.Furthermore,we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.展开更多
基金supported by the National Natural Science Foundation of China(32270564,81830032,82071421)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2018B030337001)+2 种基金Guangzhou Key Research Program on Brain Science(202007030008)Guangdong Basic and Applied Basic Research(2023A1515010811,2022A1515011205)the Fundamental Research Funds for the Central Universities(21622113).
文摘In order to dissect amyotrophic lateral sclerosis(ALS),a multigenic,multifactorial,and progressive neurodegenerative disease with heterogeneous clinical presentations,researchers have generated numerous animal models to mimic the genetic defects.Concurrent and comparative analysis of these various models allows identification of the causes and mechanisms of ALS in order to finally obtain effective therapeutics.However,most genetically modified rodent models lack overt pathological features,imposing challenges and limitations in utilizing them to rigorously test the potential mechanisms.Recent studies using large animals,including pigs and non-human primates,have uncovered important events that resemble neurodegeneration in patients’brains but could not be produced in small animals.Here we describe common features as well as discrepancies among these models,highlighting new insights from these models.Furthermore,we will discuss how to make rodent models more capable of recapitulating important pathological features based on the important pathogenic insights from large animal models.
