LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice

Honglin Tan, Mina Chen, Dejiang Pang, Xiaoqiang Xia, Chongyangzi Du, Wanchun Yang, Yiyuan Cui, Chao Huang, Wanxiang Jiang, Dandan Bi, Chunyu Li, Huifang Shang, Paul F. Worley, Bo Xiao

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Improving neuronal survival in ALS remains a significant challenge. Previously, we identified Lanthionine synthetase C-like protein 1 (LanCL1) as a neuronal antioxidant defense gene, the genetic deletion of which causes apoptotic neurodegeneration in the brain. Here, we report in vivo data using the transgenic SOD1G93A mouse model of ALS indicating that CNS-specific expression of LanCL1 transgene extends lifespan, delays disease onset, decelerates symptomatic progression, and improves motor performance of SOD1G93A mice. Conversely, CNS-specific deletion of LanCL1 leads to neurodegenerative phenotypes, including motor neuron loss, neuroinflammation, and oxidative damage. Analysis reveals that LanCL1 is a positive regulator of AKT activity, and LanCL1 overexpression restores the impaired AKT activity in ALS model mice. These findings indicate that LanCL1 regulates neuronal survival through an alternative mechanism, and suggest a new therapeutic target in ALS.

Original languageEnglish (US)
JournalCell death and differentiation
DOIs
StateAccepted/In press - Jan 1 2019

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Survival of Motor Neuron 1 Protein
Amyotrophic Lateral Sclerosis
Ligases
Protein C
Motor Neurons
Gene Deletion
Transgenes
Neurodegenerative Diseases
Transgenic Mice
lanthionine
Antioxidants
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice. / Tan, Honglin; Chen, Mina; Pang, Dejiang; Xia, Xiaoqiang; Du, Chongyangzi; Yang, Wanchun; Cui, Yiyuan; Huang, Chao; Jiang, Wanxiang; Bi, Dandan; Li, Chunyu; Shang, Huifang; Worley, Paul F.; Xiao, Bo.

In: Cell death and differentiation, 01.01.2019.

Research output: Contribution to journalArticle

Tan, H, Chen, M, Pang, D, Xia, X, Du, C, Yang, W, Cui, Y, Huang, C, Jiang, W, Bi, D, Li, C, Shang, H, Worley, PF & Xiao, B 2019, 'LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice', Cell death and differentiation. https://doi.org/10.1038/s41418-019-0422-6
Tan, Honglin ; Chen, Mina ; Pang, Dejiang ; Xia, Xiaoqiang ; Du, Chongyangzi ; Yang, Wanchun ; Cui, Yiyuan ; Huang, Chao ; Jiang, Wanxiang ; Bi, Dandan ; Li, Chunyu ; Shang, Huifang ; Worley, Paul F. ; Xiao, Bo. / LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice. In: Cell death and differentiation. 2019.
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AU - Yang, Wanchun

AU - Cui, Yiyuan

AU - Huang, Chao

AU - Jiang, Wanxiang

AU - Bi, Dandan

AU - Li, Chunyu

AU - Shang, Huifang

AU - Worley, Paul F.

AU - Xiao, Bo

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