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The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis.
Cell Physiol Biochem. 2019; 52(6):1412-1426.CP

Abstract

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.

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.

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.

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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Publisher Full Text (DOI)

Authors+Show Affiliations

Rohm M
Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Cytology, Bochum, Germany.
May C
Ruhr University Bochum, Medical Faculty, Medizinisches Proteom-Center, Bochum, Germany.
Marcus K
Ruhr University Bochum, Medical Faculty, Medizinisches Proteom-Center, Bochum, Germany.
Steinbach S
Ruhr University Bochum, Medical Faculty, Medizinisches Proteom-Center, Bochum, Germany.
Theis V
Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Cytology, Bochum, Germany.
Theiss C
Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Cytology, Bochum, Germany.
Matschke V
Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Cytology, Bochum, Germany, Veronika.Matschke@rub.de.

MeSH

Adaptor Proteins, Signal TransducingAmyotrophic Lateral SclerosisAnimalsApoptosisDisease Models, AnimalDown-RegulationIn Situ HybridizationMiceMicroRNAsMicroscopy, FluorescenceMotor NeuronsProteinsSpinal CordTumor Suppressor Protein p53

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31075191

Citation

Rohm, Marlena, et al. "The microRNA miR-375-3p and the Tumor Suppressor NDRG2 Are Involved in Sporadic Amyotrophic Lateral Sclerosis." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 52, no. 6, 2019, pp. 1412-1426.
Rohm M, May C, Marcus K, et al. The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis. Cell Physiol Biochem. 2019;52(6):1412-1426.
Rohm, M., May, C., Marcus, K., Steinbach, S., Theis, V., Theiss, C., & Matschke, V. (2019). The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 52(6), 1412-1426. https://doi.org/10.33594/000000099
Rohm M, et al. The microRNA miR-375-3p and the Tumor Suppressor NDRG2 Are Involved in Sporadic Amyotrophic Lateral Sclerosis. Cell Physiol Biochem. 2019;52(6):1412-1426. PubMed PMID: 31075191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis. AU - Rohm,Marlena, AU - May,Caroline, AU - Marcus,Katrin, AU - Steinbach,Simone, AU - Theis,Verena, AU - Theiss,Carsten, AU - Matschke,Veronika, PY - 2019/01/28/received PY - 2019/05/06/accepted PY - 2019/5/11/entrez PY - 2019/5/11/pubmed PY - 2019/5/22/medline KW - Motor neuron KW - Neurodegeneration KW - Wobbler mouse KW - miRNA KW - p53 SP - 1412 EP - 1426 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell Physiol Biochem VL - 52 IS - 6 N2 - 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. 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. 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. 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. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/31075191/The_microRNA_miR_375_3p_and_the_Tumor_Suppressor_NDRG2_are_Involved_in_Sporadic_Amyotrophic_Lateral_Sclerosis_ DB - PRIME DP - Unbound Medicine ER -