期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 8, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40478-020-00987-6
关键词
Amyotrophic lateral sclerosis; Tdp-43; Axonal transcriptome; Nicotinamide
资金
- Deutsche Forschungsgemeinschaft [BR4910/1-1 (SPP1738), BR4910/2-1 (SPP1935), SE697/4-1 (SPP1738), SE697/5-1 (SPP1935), SE697/1]
- Open Access Publication Fund of the University of Wuerzburg
Protein inclusions containing the RNA-binding protein TDP-43 are a pathological hallmark of amyotrophic lateral sclerosis and other neurodegenerative disorders. The loss of TDP-43 function that is associated with these inclusions affects post-transcriptional processing of RNAs in multiple ways including pre-mRNA splicing, nucleocytoplasmic transport, modulation of mRNA stability and translation. In contrast, less is known about the role of TDP-43 in axonal RNA metabolism in motoneurons. Here we show that depletion of Tdp-43 in primary motoneurons affects axon growth. This defect is accompanied by subcellular transcriptome alterations in the axonal and somatodendritic compartment. The axonal localization of transcripts encoding components of the cytoskeleton, the translational machinery and transcripts involved in mitochondrial energy metabolism were particularly affected by loss of Tdp-43. Accordingly, we observed reduced protein synthesis and disturbed mitochondrial functions in axons of Tdp-43-depleted motoneurons. Treatment with nicotinamide rescued the axon growth defect associated with loss of Tdp-43. These results show that Tdp-43 depletion in motoneurons affects several pathways integral to axon health indicating that loss of TDP-43 function could thus make a major contribution to axonal pathomechanisms in ALS.
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。
推荐
暂无数据