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The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis.
Rohm, Marlena; May, Caroline; Marcus, Katrin; Steinbach, Simone; Theis, Verena; Theiss, Carsten; Matschke, Veronika.
  • 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.
Cell Physiol Biochem ; 52(6): 1412-1426, 2019.
Article en En | MEDLINE | ID: mdl-31075191
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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas / MicroARNs Límite: Animals Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas / MicroARNs Límite: Animals Idioma: En Año: 2019 Tipo del documento: Article