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Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models

Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains...

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Autores principales: Miller, John A., Drouet, Domenica E., Yermakov, Leonid M., Elbasiouny, Mahmoud S., Bensabeur, Fatima Z., Bottomley, Michael, Susuki, Keiichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737575/
https://www.ncbi.nlm.nih.gov/pubmed/36499770
http://dx.doi.org/10.3390/ijms232315443
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author Miller, John A.
Drouet, Domenica E.
Yermakov, Leonid M.
Elbasiouny, Mahmoud S.
Bensabeur, Fatima Z.
Bottomley, Michael
Susuki, Keiichiro
author_facet Miller, John A.
Drouet, Domenica E.
Yermakov, Leonid M.
Elbasiouny, Mahmoud S.
Bensabeur, Fatima Z.
Bottomley, Michael
Susuki, Keiichiro
author_sort Miller, John A.
collection PubMed
description Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains, a family of calcium dependent cysteine proteases, have been shown to have a role in developmental myelination and in demyelinating diseases. The roles of calpains in myelination and demyelination in the peripheral nervous system remain unclear. Here, we show a transient increase of activated CAPN1, a major calpain isoform, in postnatal rat sciatic nerves when myelin is actively formed. Expression of the endogenous calpain inhibitor, calpastatin, showed a steady decrease throughout the period of peripheral nerve development. In the sciatic nerves of Trembler-J mice characterized by dysmyelination, expression levels of CAPN1 and calpastatin and calpain activity were significantly increased. In lysolecithin-induced acute demyelination in adult rat sciatic nerves, we show an increase of CAPN1 and decrease of calpastatin expression. These changes in the calpain-calpastatin system are distinct from those during central nervous system development or in acute axonal degeneration in peripheral nerves. Our results suggest that the calpain-calpastatin system has putative roles in myelination and demyelinating diseases of peripheral nerves.
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spelling pubmed-97375752022-12-11 Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models Miller, John A. Drouet, Domenica E. Yermakov, Leonid M. Elbasiouny, Mahmoud S. Bensabeur, Fatima Z. Bottomley, Michael Susuki, Keiichiro Int J Mol Sci Article Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains, a family of calcium dependent cysteine proteases, have been shown to have a role in developmental myelination and in demyelinating diseases. The roles of calpains in myelination and demyelination in the peripheral nervous system remain unclear. Here, we show a transient increase of activated CAPN1, a major calpain isoform, in postnatal rat sciatic nerves when myelin is actively formed. Expression of the endogenous calpain inhibitor, calpastatin, showed a steady decrease throughout the period of peripheral nerve development. In the sciatic nerves of Trembler-J mice characterized by dysmyelination, expression levels of CAPN1 and calpastatin and calpain activity were significantly increased. In lysolecithin-induced acute demyelination in adult rat sciatic nerves, we show an increase of CAPN1 and decrease of calpastatin expression. These changes in the calpain-calpastatin system are distinct from those during central nervous system development or in acute axonal degeneration in peripheral nerves. Our results suggest that the calpain-calpastatin system has putative roles in myelination and demyelinating diseases of peripheral nerves. MDPI 2022-12-06 /pmc/articles/PMC9737575/ /pubmed/36499770 http://dx.doi.org/10.3390/ijms232315443 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Miller, John A.
Drouet, Domenica E.
Yermakov, Leonid M.
Elbasiouny, Mahmoud S.
Bensabeur, Fatima Z.
Bottomley, Michael
Susuki, Keiichiro
Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title_full Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title_fullStr Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title_full_unstemmed Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title_short Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models
title_sort distinct changes in calpain and calpastatin during pns myelination and demyelination in rodent models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737575/
https://www.ncbi.nlm.nih.gov/pubmed/36499770
http://dx.doi.org/10.3390/ijms232315443
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