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Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction

Some patients experience impaired cognitive functioning after surgery, a phenomenon referred to as postoperative cognitive dysfunction (POCD). Signs of POCD are closely associated with the development of systemic or hippocampal inflammation. However, the precise pathophysiological mechanisms of prev...

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Autores principales: Cheon, So Yeong, Kim, Jeong Min, Kam, Eun Hee, Ho, Chun-Chang, Kim, Eun Jung, Chung, Seungsoo, Jeong, Ji-Hyun, Lee, Diane Da-Hyun, Lee, Sang-Won, Koo, Bon-Nyeo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647420/
https://www.ncbi.nlm.nih.gov/pubmed/29044209
http://dx.doi.org/10.1038/s41598-017-14027-2
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author Cheon, So Yeong
Kim, Jeong Min
Kam, Eun Hee
Ho, Chun-Chang
Kim, Eun Jung
Chung, Seungsoo
Jeong, Ji-Hyun
Lee, Diane Da-Hyun
Lee, Sang-Won
Koo, Bon-Nyeo
author_facet Cheon, So Yeong
Kim, Jeong Min
Kam, Eun Hee
Ho, Chun-Chang
Kim, Eun Jung
Chung, Seungsoo
Jeong, Ji-Hyun
Lee, Diane Da-Hyun
Lee, Sang-Won
Koo, Bon-Nyeo
author_sort Cheon, So Yeong
collection PubMed
description Some patients experience impaired cognitive functioning after surgery, a phenomenon referred to as postoperative cognitive dysfunction (POCD). Signs of POCD are closely associated with the development of systemic or hippocampal inflammation. However, the precise pathophysiological mechanisms of prevention/treatment options for POCD still remain unclear. After injury, the transcriptional factor nuclear factor-kappa B (NF-κB) is thought to regulate or stimulate inflammation amplification. Therefore, we designed a cell-penetrating fusion protein called nt-p65-TMD, which inhibits NF-κB p65 activation by translocating into the nucleus. In the present study, we discovered that nt-p65-TMD exerted effects on surgery-induced cognitive impairment in mice. Specifically, nt-p65-TMD exhibited strong immunoregulatory properties that were able to reduce surgery-induced elevations in cerebrovascular integrity impairment, subsequent peripheral immune-cell recruitment, and inflammation amplification, which ultimately lead to cognitive decline. The nt-p65-TMD has the unique ability to regulate and reduce systemic inflammation and inflammation amplification, suggesting a new strategy for preventing development of cognitive decline that occurs in POCD.
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spelling pubmed-56474202017-10-26 Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction Cheon, So Yeong Kim, Jeong Min Kam, Eun Hee Ho, Chun-Chang Kim, Eun Jung Chung, Seungsoo Jeong, Ji-Hyun Lee, Diane Da-Hyun Lee, Sang-Won Koo, Bon-Nyeo Sci Rep Article Some patients experience impaired cognitive functioning after surgery, a phenomenon referred to as postoperative cognitive dysfunction (POCD). Signs of POCD are closely associated with the development of systemic or hippocampal inflammation. However, the precise pathophysiological mechanisms of prevention/treatment options for POCD still remain unclear. After injury, the transcriptional factor nuclear factor-kappa B (NF-κB) is thought to regulate or stimulate inflammation amplification. Therefore, we designed a cell-penetrating fusion protein called nt-p65-TMD, which inhibits NF-κB p65 activation by translocating into the nucleus. In the present study, we discovered that nt-p65-TMD exerted effects on surgery-induced cognitive impairment in mice. Specifically, nt-p65-TMD exhibited strong immunoregulatory properties that were able to reduce surgery-induced elevations in cerebrovascular integrity impairment, subsequent peripheral immune-cell recruitment, and inflammation amplification, which ultimately lead to cognitive decline. The nt-p65-TMD has the unique ability to regulate and reduce systemic inflammation and inflammation amplification, suggesting a new strategy for preventing development of cognitive decline that occurs in POCD. Nature Publishing Group UK 2017-10-18 /pmc/articles/PMC5647420/ /pubmed/29044209 http://dx.doi.org/10.1038/s41598-017-14027-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cheon, So Yeong
Kim, Jeong Min
Kam, Eun Hee
Ho, Chun-Chang
Kim, Eun Jung
Chung, Seungsoo
Jeong, Ji-Hyun
Lee, Diane Da-Hyun
Lee, Sang-Won
Koo, Bon-Nyeo
Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title_full Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title_fullStr Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title_full_unstemmed Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title_short Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction
title_sort cell-penetrating interactomic inhibition of nuclear factor-kappa b in a mouse model of postoperative cognitive dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647420/
https://www.ncbi.nlm.nih.gov/pubmed/29044209
http://dx.doi.org/10.1038/s41598-017-14027-2
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