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LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models
Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the LAMA2 gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy aff...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190814/ https://www.ncbi.nlm.nih.gov/pubmed/32390798 http://dx.doi.org/10.3389/fnmol.2020.00060 |
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author | Previtali, Stefano Carlo Zambon, Alberto Andrea |
author_facet | Previtali, Stefano Carlo Zambon, Alberto Andrea |
author_sort | Previtali, Stefano Carlo |
collection | PubMed |
description | Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the LAMA2 gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a developmentally-associated dysmyelinating neuropathy that contributes to the disease progression, in addition to brain abnormalities; the latter often underappreciated. In this brief review, we present data supporting the impact of peripheral neuropathy in the LAMA2-RD phenotype, including both mouse models and human studies. We discuss the molecular mechanisms underlying nerve abnormalities and involved in the laminin-211 pathway, which affects axon sorting, ensheathing and myelination. We conclude with some final considerations of consequences on nerve regeneration and potential therapeutic strategies. |
format | Online Article Text |
id | pubmed-7190814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71908142020-05-08 LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models Previtali, Stefano Carlo Zambon, Alberto Andrea Front Mol Neurosci Neuroscience Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the LAMA2 gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a developmentally-associated dysmyelinating neuropathy that contributes to the disease progression, in addition to brain abnormalities; the latter often underappreciated. In this brief review, we present data supporting the impact of peripheral neuropathy in the LAMA2-RD phenotype, including both mouse models and human studies. We discuss the molecular mechanisms underlying nerve abnormalities and involved in the laminin-211 pathway, which affects axon sorting, ensheathing and myelination. We conclude with some final considerations of consequences on nerve regeneration and potential therapeutic strategies. Frontiers Media S.A. 2020-04-23 /pmc/articles/PMC7190814/ /pubmed/32390798 http://dx.doi.org/10.3389/fnmol.2020.00060 Text en Copyright © 2020 Previtali and Zambon. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Previtali, Stefano Carlo Zambon, Alberto Andrea LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title | LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title_full | LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title_fullStr | LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title_full_unstemmed | LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title_short | LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models |
title_sort | lama2 neuropathies: human findings and pathomechanisms from mouse models |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190814/ https://www.ncbi.nlm.nih.gov/pubmed/32390798 http://dx.doi.org/10.3389/fnmol.2020.00060 |
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