Infantile-onset spinal muscular atrophy is the quintessential example of a disorder characterized by a predominantly neurodegenerative phenotype that nevertheless stems from perturbations in a housekeeping protein.Res...Infantile-onset spinal muscular atrophy is the quintessential example of a disorder characterized by a predominantly neurodegenerative phenotype that nevertheless stems from perturbations in a housekeeping protein.Resulting from low levels of the Survival of Motor Neuron(SMN)protein,spinal muscular atrophy manifests mainly as a lower motor neuron disease.Why this is so and whether other cell types contribute to the classic spinal muscular atrophy phenotype continue to be the subject of intense investigation and are only now gaining appreciation.Yet,what is emerging is sometimes as puzzling as it is instructive,arguing for a careful re-examination of recent study outcomes,raising questions about established dogma in the field and making the case for a greater focus on milder spinal muscular atrophy models as tools to identify key mechanisms driving selective neuromuscular dysfunction in the disease.This review examines the evidence for novel molecular and cellular mechanisms that have recently been implicated in spinal muscular atrophy,highlights breakthroughs,points out caveats and poses questions that ought to serve as the basis of new investigations to better understand and treat this and other more common neurodegenerative disorders.展开更多
Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replic...Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replicability in behavioral findings.As we have discussed in our recent publication (Cho et al.,2021),in the htau mouse model,the cognitive impairment reported in the original study has not been consistently replicated by different labs over the past decade.This variability in behavioral findings seems to exist in many,if not all,AD mouse models that have been behaviorally evaluated.展开更多
基金Research on SMA in the Monani lab is funded by NIH(R21 NS099921,R01 NS104218)Cure SMA and Roche Inc(to URM).
文摘Infantile-onset spinal muscular atrophy is the quintessential example of a disorder characterized by a predominantly neurodegenerative phenotype that nevertheless stems from perturbations in a housekeeping protein.Resulting from low levels of the Survival of Motor Neuron(SMN)protein,spinal muscular atrophy manifests mainly as a lower motor neuron disease.Why this is so and whether other cell types contribute to the classic spinal muscular atrophy phenotype continue to be the subject of intense investigation and are only now gaining appreciation.Yet,what is emerging is sometimes as puzzling as it is instructive,arguing for a careful re-examination of recent study outcomes,raising questions about established dogma in the field and making the case for a greater focus on milder spinal muscular atrophy models as tools to identify key mechanisms driving selective neuromuscular dysfunction in the disease.This review examines the evidence for novel molecular and cellular mechanisms that have recently been implicated in spinal muscular atrophy,highlights breakthroughs,points out caveats and poses questions that ought to serve as the basis of new investigations to better understand and treat this and other more common neurodegenerative disorders.
文摘Alzheimer's disease (AD) mouse models have proven to be an invaluable tool for deepening our understanding of disease mechanisms and for developing therapeutics.However,one common frustration is the lack of replicability in behavioral findings.As we have discussed in our recent publication (Cho et al.,2021),in the htau mouse model,the cognitive impairment reported in the original study has not been consistently replicated by different labs over the past decade.This variability in behavioral findings seems to exist in many,if not all,AD mouse models that have been behaviorally evaluated.
