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A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice

It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprote...

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Autores principales: Liu, Lin, Liu, Kai-Jie, Cao, Jian-Bo, Yang, Jing, Yu, Hua-Li, He, Xiao-Xiao, He, Zi-Xuan, Zhu, Xiao-Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125294/
https://www.ncbi.nlm.nih.gov/pubmed/34063230
http://dx.doi.org/10.3390/ijms22094829
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author Liu, Lin
Liu, Kai-Jie
Cao, Jian-Bo
Yang, Jing
Yu, Hua-Li
He, Xiao-Xiao
He, Zi-Xuan
Zhu, Xiao-Juan
author_facet Liu, Lin
Liu, Kai-Jie
Cao, Jian-Bo
Yang, Jing
Yu, Hua-Li
He, Xiao-Xiao
He, Zi-Xuan
Zhu, Xiao-Juan
author_sort Liu, Lin
collection PubMed
description It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1′s EGF3 domain (residues 407–422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH.
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spelling pubmed-81252942021-05-17 A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice Liu, Lin Liu, Kai-Jie Cao, Jian-Bo Yang, Jing Yu, Hua-Li He, Xiao-Xiao He, Zi-Xuan Zhu, Xiao-Juan Int J Mol Sci Article It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1′s EGF3 domain (residues 407–422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH. MDPI 2021-05-02 /pmc/articles/PMC8125294/ /pubmed/34063230 http://dx.doi.org/10.3390/ijms22094829 Text en © 2021 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
Liu, Lin
Liu, Kai-Jie
Cao, Jian-Bo
Yang, Jing
Yu, Hua-Li
He, Xiao-Xiao
He, Zi-Xuan
Zhu, Xiao-Juan
A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title_full A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title_fullStr A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title_full_unstemmed A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title_short A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice
title_sort novel netrin-1-derived peptide enhances protection against neuronal death and mitigates of intracerebral hemorrhage in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125294/
https://www.ncbi.nlm.nih.gov/pubmed/34063230
http://dx.doi.org/10.3390/ijms22094829
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