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

 So Yeong Cheon  ;  Jeong Min Kim  ;  Eun Hee Kam  ;  Chun-Chang Ho  ;  Eun Jung Kim  ;  Seungsoo Chung  ;  Ji-Hyun Jeong  ;  Diane Da-Hyun Lee  ;  Sang-Won Lee  ;  Bon-Nyeo Koo 
 Scientific Reports, Vol.7(1) : 13482, 2017 
Journal Title
 Scientific Reports 
Issue Date
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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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
구본녀(Koo, Bon-Nyeo) ORCID logo https://orcid.org/0000-0002-3189-1673
김은정(Kim, Eun Jung) ORCID logo https://orcid.org/0000-0002-5693-1336
김정민(Kim, Jeongmin) ORCID logo https://orcid.org/0000-0002-0468-8012
이상원(Lee, Sang Won) ORCID logo https://orcid.org/0000-0002-8038-3341
정승수(Chung, Seung Soo) ORCID logo https://orcid.org/0000-0002-3119-9628
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