eprintid: 10092027
rev_number: 22
eprint_status: archive
userid: 608
dir: disk0/10/09/20/27
datestamp: 2020-02-26 14:12:51
lastmod: 2021-09-20 22:33:03
status_changed: 2020-02-26 14:12:51
type: article
metadata_visibility: show
creators_name: Mòdol-Caballero, G
creators_name: Herrando-Grabulosa, M
creators_name: García-Lareu, B
creators_name: Solanes, N
creators_name: Verdés, S
creators_name: Osta, R
creators_name: Francos-Quijorna, I
creators_name: López-Vales, R
creators_name: Calvo, AC
creators_name: Bosch, A
creators_name: Navarro, X
title: Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D77
keywords: Amyotrophic lateral sclerosis, ErbB receptors, Motoneuron, Motor function, Neuregulin 1, Neuromuscular junction, Spinal cord
note: © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motoneurons (MNs), with no effective treatment currently available. The molecular mechanisms that are involved in MN death are complex and not fully understood, with partial contributions of surrounding glial cells and skeletal muscle to the disease. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. Recent studies have suggested a crucial role of the isoform I (NRG1-I) in the collateral reinnervation process in skeletal muscle, and NRG1-III in the preservation of MNs in the spinal cord, opening a window for developing novel therapies for neuromuscular diseases like ALS. In this study, we overexpressed NRG1-I widely in the skeletal muscles of the SOD1G93A transgenic mouse. The results show that NRG1 gene therapy activated the survival pathways in muscle and spinal cord, increasing the number of surviving MNs and neuromuscular junctions and reducing the astroglial reactivity in the spinal cord of the treated SOD1G93A mice. Furthermore, NRG1-I overexpression preserved motor function and delayed the onset of clinical disease. In summary, our data indicates that NRG1 plays an important role on MN survival and muscle innervation in ALS, and that viral-mediated overexpression of NRG1 isoforms may be considered as a promising approach for ALS treatment.
date: 2020-02-04
date_type: published
official_url: http://dx.doi.org/10.1016/j.nbd.2020.104793
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1751032
doi: 10.1016/j.nbd.2020.104793
pii: S0969-9961(20)30068-1
lyricists_name: Modol Caballero, Guillem
lyricists_id: GMODO51
actors_name: Modol Caballero, Guillem
actors_id: GMODO51
actors_role: owner
full_text_status: public
publication: Neurobiology of Disease
volume: 137
article_number: 104793
event_location: United States
citation:        Mòdol-Caballero, G;    Herrando-Grabulosa, M;    García-Lareu, B;    Solanes, N;    Verdés, S;    Osta, R;    Francos-Quijorna, I;                 ... Navarro, X; + view all <#>        Mòdol-Caballero, G;  Herrando-Grabulosa, M;  García-Lareu, B;  Solanes, N;  Verdés, S;  Osta, R;  Francos-Quijorna, I;  López-Vales, R;  Calvo, AC;  Bosch, A;  Navarro, X;   - view fewer <#>    (2020)    Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice.                   Neurobiology of Disease , 137     , Article 104793.  10.1016/j.nbd.2020.104793 <https://doi.org/10.1016/j.nbd.2020.104793>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10092027/3/Modol%20Caballero_1-s2.0-S0969996120300681-main.pdf