The microRNA miR-375-3p and the Tumor Suppressor NDRG2 are Involved in Sporadic Amyotrophic Lateral Sclerosis.
Adaptor Proteins, Signal Transducing
Amyotrophic Lateral Sclerosis
/ metabolism
Animals
Apoptosis
Disease Models, Animal
Down-Regulation
In Situ Hybridization
Mice
MicroRNAs
/ metabolism
Microscopy, Fluorescence
Motor Neurons
/ metabolism
Proteins
/ genetics
Spinal Cord
/ metabolism
Tumor Suppressor Protein p53
/ metabolism
Motor neuron
Neurodegeneration
Wobbler mouse
miRNA
p53
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
01
2019
accepted:
06
05
2019
entrez:
11
5
2019
pubmed:
11
5
2019
medline:
22
5
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Substances chimiques
Adaptor Proteins, Signal Transducing
0
MicroRNAs
0
Mirn375 microRNA, mouse
0
Ndr2 protein, mouse
0
Proteins
0
Trp53 protein, mouse
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1412-1426Subventions
Organisme : FoRUM
ID : F874N-2016
Pays : Germany
Organisme : Heinrich and Alma Vogelsang Scholarship
Pays : Germany
Organisme : German Federal Ministry of Education and Research
ID : FKZ 01DN14023
Pays : Germany
Organisme : PURE, Ministry of Culture and Science North Rhine-Westfalia
ID : 233-1.08.03.03-031-68079
Pays : Germany
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors state that there are no personal or institutional conflicts of interest.