Neurotoxicity Research

, Volume 33, Issue 4, pp 693–701 | Cite as

Purα Repaired Expanded Hexanucleotide GGGGCC Repeat Noncoding RNA-Caused Neuronal Toxicity in Neuro-2a Cells

ORIGINAL ARTICLE
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Abstract

Expanded hexanucleotide GGGGCC repeat in a noncoding region of C9ORF72 is the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, its molecular pathogenesis remains unclear. In our previous study, the expanded GGGGCC repeats have been shown to be sufficient to cause neurodegeneration. In order to investigate the further role of expanded GGGGCC repeats in the neuron, the normal r(GGGGCC)3 and mutant-type expanded r(GGGGCC)30 expression vectors were transfected into Neuro-2a cells. Cell proliferation, dendrite development, and the proteins’ levels of microtubule-associated protein-2 (MAP2) and cyclin-dependent kinase-5 (CDK5) were used to evaluate the cell toxicity of GGGGCC repeats on Neuro-2a cells. The results were shown that expression of expanded GGGGCC repeats caused neuronal cell toxicity in Neuro-2a cells, enhanced the expression of pMAP2 and pCDK5. Moreover, overexpression of Purα repaired expanded GGGGCC repeat-inducing neuronal toxicity in Neuro-2a cells and reduced the expression of pMAP2 and pCDK5. In all, our findings suggested that the expanded GGGGCC repeats might cause neurodegeneration through destroyed neuron cells. And the GGGGCC repeat-induced neuronal cell toxicity was inhibited by upregulation of Purα. We inferred that Purα inhibits expanded GGGGCC repeat-inducing neurodegeneration, which might reveal a novel mechanism of neurodegenerative diseases ALS and FTD.

Keywords

GGGGCC repeat ALS FTD Neurodegeneration Neuro-2a 
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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31400916 and no. 81370942), Natural Science Foundation of Hubei Province (No. 2014CFB219), and Youth Science Chenguang Plan of Wuhan City (No. 2015071704011624). We thank professor Peng Jin of Emory University for providing plasmids pEGFP-N1-(GGGGCC)3 and pEGFP-N1-(GGGGCC)30.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Histology and Embryology, Department of Anatomy, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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