The microRNA miR-375-3p and the tumor suppressor NDRG2 are involved in sporadic amyotrophic lateral sclerosis

  • \(\bf Background/Aims:\) Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in humans. However, the pathogenesis of ALS is not yet understood. The wobbler mouse is considered as an animal model for the sporadic form of ALS due to its spontaneous mutation in the Vps54 gene. Due to transactivation of NDRG2 by p53, this tumor suppressor might play a functional role in stress induced cell death in wobbler mice as well as ALS patients. Furthermore, deregulated microRNAs are often related to neurodegenerative diseases. Thus, the NDRG2 linked miR-375-3p was of interest for this study. \(\bf Methods:\) Here, we investigated the relevance of NDRG2 and miR-375-3p for the pathomechanism of the motor neuronal degeneration in wobbler mice by investigating expression level via qPCR and Western Blot as well as localization of these molecules in the cervical spinal cord by in situ hybridization, immunostaining and mass spectrometric analysis. \(\bf Results:\) We were able to show a differential regulation of the expression of NDRG2 as well as miR-375-3p in the cervical part of the spinal cord of wobbler mice. In addition, for the first time we were able to demonstrate an expression of NDRG2 in motor neurons using different techniques. \(\bf Conclusion:\) The present study has shown NDRG2 and miR-375-3p to be promising targets for further research of the pathogenesis of sporadic ALS in the wobbler mouse model. Based on these results and in combination with previous published data we could develop a putative pro-apoptotic mechanism in the spinal cord of the wobbler mouse.

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Metadaten
Author:Marlena RohmORCiDGND, Caroline MayORCiDGND, Katrin Marcus-AlicORCiDGND, Simone SteinbachGND, Verena TheisGND, Carsten TheißORCiDGND, Veronika MatschkeORCiDGND
URN:urn:nbn:de:hbz:294-71961
DOI:https://doi.org/10.33594/000000099
Parent Title (English):Cellular physiology and biochemistry
Document Type:Article
Language:English
Date of Publication (online):2020/05/29
Date of first Publication:2019/05/11
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Neurodegeneration; Open Access Fonds
Motor neuron; Wobbler mouse; miRNA; p53
Volume:52
Issue:6
First Page:1412
Last Page:1426
Note:
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Institut für Anatomie, Abteilung für Cytologie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY-NC-ND 4.0 - Attribution-NonCommercial-NoDerivatives 4.0 International