4.7 Article

Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models

期刊

ISCIENCE
卷 24, 期 11, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2021.103376

关键词

-

资金

  1. German Research Foundation [SI-1969/2-1, SI-1969/3-1, Wi 945/17-1, 431549029, 233886668, FOR 2722, 407176282, CRC1451, GRK1960]
  2. SMA-Europe
  3. European Research Council (ERC) under the European Union [956185]
  4. Center for Molecular Medicine Cologne [C18]
  5. Marie Curie Actions (MSCA) [956185] Funding Source: Marie Curie Actions (MSCA)

向作者/读者索取更多资源

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. By comparing the motor circuit pathology of three SMA mouse models, researchers have identified central excitatory synaptopathy as a key feature of motor circuit pathology in SMA, providing insight for future studies.
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. Recently, SMN dysfunction has been linked to individual aspects of motor circuit pathology in a severe SMA mouse model. To determine whether these disease mechanisms are conserved, we directly compared the motor circuit pathology of three SMA mouse models. The severe SMND7 model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, the Taiwanese model shows very mild motor neuron pathology, but early central synaptic loss. In the intermediate Smn(2B)(/-) model, strong pathology of central excitatory synapses and NMJs precedes the late onset of p53-dependent motor neuron death. These pathological events correlate with SMN-dependent splicing dysregulation of specific mRNAs. Our study provides a knowledge base for properly tailoring future studies and identifies central excitatory synaptopathy as a key feature of motor circuit pathology in SMA.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据