miR-206 Reduces the Severity of Motor Neuron Degeneration in the Facial Nuclei of the Brainstem in a Mouse Model of SMA.
Brainstem
NCX2
miR-206
motor neuron disease
spinal muscular atrophy
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
26
07
2019
revised:
02
01
2020
accepted:
02
01
2020
pubmed:
23
2
2020
medline:
7
4
2021
entrez:
21
2
2020
Statut:
ppublish
Résumé
Spinal muscular atrophy (SMA) is a severe neuromuscular disease affecting infants caused by alterations of the survival motor neuron gene, which results in progressive degeneration of motor neurons (MNs). Although an effective treatment for SMA patients has been recently developed, the molecular pathway involved in selective MN degeneration has not been yet elucidated. In particular, miR-206 has been demonstrated to play a relevant role in the regeneration of neuromuscular junction in several MN diseases, and particularly it is upregulated in the quadriceps, tibialis anterior, spinal cord, and serum of SMA mice. In the present paper, we demonstrated that miR-206 was transiently upregulated also in the brainstem of the mouse model of SMA, SMAΔ7, in the early phase of the disease paralleling MN degeneration and was down-regulated in the late symptomatic phase. To prevent this downregulation, we intracerebroventricularly injected miR-206 in SMA pups, demonstrating that miR-206 reduced the severity of SMA pathology, slowing down disease progression, increasing survival rate, and improving behavioral performance of mice. Interestingly, exogenous miRNA-206-induced upregulation caused a reduction of the predicted target sodium calcium exchanger isoform 2, NCX2, one of the main regulators of intracellular [Ca
Identifiants
pubmed: 32075715
pii: S1525-0016(20)30037-X
doi: 10.1016/j.ymthe.2020.01.013
pmc: PMC7132835
pii:
doi:
Substances chimiques
MIRN206 microRNA, human
0
MicroRNAs
0
Slc8a2 protein, mouse
0
Sodium-Calcium Exchanger
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1154-1166Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
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