Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics
Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These mutations result in the complete absence or truncated expression of the laminin-α2 chain. The α2-chain is a major component of the laminin-211 and laminin-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2020.00001/full |
| _version_ | 1819017860134993920 |
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| author | Pamela Barraza-Flores Christina R. Bates Ariany Oliveira-Santos Dean J. Burkin |
| author_facet | Pamela Barraza-Flores Christina R. Bates Ariany Oliveira-Santos Dean J. Burkin |
| author_sort | Pamela Barraza-Flores |
| collection | DOAJ |
| description | Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These mutations result in the complete absence or truncated expression of the laminin-α2 chain. The α2-chain is a major component of the laminin-211 and laminin-221 isoforms, the predominant laminin isoforms in healthy adult skeletal muscle. Mutations in this chain result in progressive skeletal muscle degeneration as early as neonatally. Laminin-211/221 is a ligand for muscle cell receptors integrin-α7β1 and α-dystroglycan. LAMA2 mutations are correlated with integrin-α7β1 disruption in skeletal muscle. In this review, we will summarize laminin-211/221 interactions with integrin-α7β1 in LAMA2-CMD muscle. Additionally, we will summarize recent developments using upregulation of laminin-111 in the sarcolemma of laminin-α2-deficient muscle. We will discuss potential mechanisms of action by which laminin-111 is able to prevent myopathy. These published studies demonstrate that laminin-111 is a disease modifier of LAMA2-CMD through different methods of delivery. Together, these studies show the potential for laminin-111 therapy as a novel paradigm for the treatment of LAMA2-CMD. |
| first_indexed | 2024-12-21T03:10:14Z |
| format | Article |
| id | doaj.art-7123fb1512804142b1393b64f4d36749 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-21T03:10:14Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-7123fb1512804142b1393b64f4d367492022-12-21T19:18:01ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-02-011310.3389/fnmol.2020.00001501084Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to TherapeuticsPamela Barraza-FloresChristina R. BatesAriany Oliveira-SantosDean J. BurkinLaminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These mutations result in the complete absence or truncated expression of the laminin-α2 chain. The α2-chain is a major component of the laminin-211 and laminin-221 isoforms, the predominant laminin isoforms in healthy adult skeletal muscle. Mutations in this chain result in progressive skeletal muscle degeneration as early as neonatally. Laminin-211/221 is a ligand for muscle cell receptors integrin-α7β1 and α-dystroglycan. LAMA2 mutations are correlated with integrin-α7β1 disruption in skeletal muscle. In this review, we will summarize laminin-211/221 interactions with integrin-α7β1 in LAMA2-CMD muscle. Additionally, we will summarize recent developments using upregulation of laminin-111 in the sarcolemma of laminin-α2-deficient muscle. We will discuss potential mechanisms of action by which laminin-111 is able to prevent myopathy. These published studies demonstrate that laminin-111 is a disease modifier of LAMA2-CMD through different methods of delivery. Together, these studies show the potential for laminin-111 therapy as a novel paradigm for the treatment of LAMA2-CMD.https://www.frontiersin.org/article/10.3389/fnmol.2020.00001/fullLAMA2-CMDLamininα7 integrinmuscular dystrophymuscletherapeutic |
| spellingShingle | Pamela Barraza-Flores Christina R. Bates Ariany Oliveira-Santos Dean J. Burkin Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics Frontiers in Molecular Neuroscience LAMA2-CMD Laminin α7 integrin muscular dystrophy muscle therapeutic |
| title | Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics |
| title_full | Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics |
| title_fullStr | Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics |
| title_full_unstemmed | Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics |
| title_short | Laminin and Integrin in LAMA2-Related Congenital Muscular Dystrophy: From Disease to Therapeutics |
| title_sort | laminin and integrin in lama2 related congenital muscular dystrophy from disease to therapeutics |
| topic | LAMA2-CMD Laminin α7 integrin muscular dystrophy muscle therapeutic |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2020.00001/full |
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