0 23

Cited 0 times in

Repositioning of niclosamide ethanolamine (NEN), an anthelmintic drug, for the treatment of lipotoxicity

Authors
 Jeong Su Park  ;  Yu Seol Lee  ;  Da Hyun Lee  ;  Soo HanBae 
Citation
 Free Radical Biology and Medicine, Vol.137 : 143-157, 2019 
Journal Title
 Free Radical Biology and Medicine 
ISSN
 0891-5849 
Issue Date
2019
Keywords
Lipotoxicity ; NASH ;  NEN ; Nrf2 ; p62
Abstract
Nonalcoholic steatohepatitis (NASH) is a common liver disease associated with metabolic disorders, including obesity and type 2 diabetes (T2D). Despite its worldwide prevalence, there are no effective drugs for the treatment of NASH. The progression of NASH is mainly accelerated by reactive oxygen species (ROS)-induced lipotoxicity. The transcription factor known as nuclear factor erythroid 2-related factor 2 (Nrf2) is pivotal for the elimination of ROS. Accordingly, activators of Nrf2 have been implicated as promising therapeutic targets for the treatment of NASH. Niclosamide (ethanolamine salt; NEN), a drug approved by the US Food and Drug Administration (USFDA), is currently used as an anthelmintic drug for the treatment of parasitic infections. Recently, NEN was shown to improve hepatic steatosis in high-fat diet (HFD)-fed mice. However, the underlying mechanism of its antioxidant function in NASH remains unknown. Here, we demonstrate that NENinduces AMPK-mediated phosphorylation of p62 at S351 that can lead to noncanonical Nrf2 activation. We also demonstrate that NENprotects cells and mouse liver from acute lipotoxic stress through activating p62-dependent Keap1-Nrf2 pathway. Taken together, NEN can be used for clinical applications and has the potential to provide a new therapeutic option for NASH.
Full Text
https://www.sciencedirect.com/science/article/pii/S0891584919302837
DOI
10.1016/j.freeradbiomed.2019.04.030
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Jeong Su(박정수) ORCID logo https://orcid.org/0000-0003-4551-4294
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170212
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse