PMID- 23651659
OWN - NLM
STAT- MEDLINE
DCOM- 20130820
LR  - 20211021
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 92
IP  - 23
DP  - 2013 Jun 21
TI  - Therapeutic activity of inhibition of the soluble epoxide hydrolase in a mouse 
      model of scrapie.
PG  - 1145-50
LID - S0024-3205(13)00239-7 [pii]
LID - 10.1016/j.lfs.2013.04.014 [doi]
AB  - AIMS: The misfolding and the aggregation of specific proteins are key features of 
      neurodegenerative diseases, specifically Transmissible Spongiform 
      Encephalopathies (TSEs). In TSEs, neuronal loss and inflammation are associated 
      with the accumulation of the misfolded isoform (PrP(sc)) of the cellular prion 
      protein (PrP(c)). Therefore we tested the hypothesis that augmenting a natural 
      anti-inflammatory pathway mediated by epoxygenated fatty acids (EpFAs) will delay 
      lethality. EpFAs are highly potent but enzymatically labile molecules produced by 
      the actions of a number of cytochrome P450 enzymes. Stabilization of these 
      bioactive lipids by inhibiting their degradation mediated by the soluble epoxide 
      hydrolase (sEH) results in potent anti-inflammatory effects in multiple disease 
      models. MAIN METHODS: Mice were infected with the mouse-adapted RML strain of 
      scrapie by intracerebral or intraperitoneal routes. Animals received the sEH 
      inhibitor, by oral route, administrated in drinking water or vehicle (PEG400). 
      Infected mice were euthanized at a standard clinical end point. 
      Histopathological, immunohistochemical and Western blot analyses of brain tissue 
      confirmed the presence of pathology related to prion infection. KEY FINDINGS: 
      Oral administration of the sEHI did not affect the very short survival time of 
      the intracerebral prion infection group. However, mice infected by 
      intraperitoneal route and treated with t-AUCB survived significantly longer than 
      the control group mice (p<0.001). SIGNIFICANCE: These findings support the idea 
      that inhibition of sEH or augmentation of the natural EpFA signaling in the brain 
      offers a potential and different route to understand prion diseases and may 
      become a therapeutic strategy for diseases involving neuroinflammation.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Poli, Giorgio
AU  - Poli G
AD  - Department of Veterinary Science and Public Health, Faculty of Veterinary 
      Medicine, University of Milan, Milan, Italy.
FAU - Corda, Erica
AU  - Corda E
FAU - Martino, Piera Anna
AU  - Martino PA
FAU - Dall'ara, Paola
AU  - Dall'ara P
FAU - Bareggi, Silvio R
AU  - Bareggi SR
FAU - Bondiolotti, Giampietro
AU  - Bondiolotti G
FAU - Iulini, Barbara
AU  - Iulini B
FAU - Mazza, Maria
AU  - Mazza M
FAU - Casalone, Cristina
AU  - Casalone C
FAU - Hwang, Sung Hee
AU  - Hwang SH
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Inceoglu, Bora
AU  - Inceoglu B
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - U54 NS079202/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130505
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid)
RN  - 0 (Benzoates)
RN  - 0 (Prions)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Benzoates/pharmacology/therapeutic use
MH  - Blotting, Western
MH  - Brain/pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Epoxide Hydrolases/*antagonists & inhibitors/physiology
MH  - Female
MH  - Injections, Intraperitoneal
MH  - Injections, Intraventricular
MH  - Mice
MH  - Prions/administration & dosage/drug effects
MH  - Scrapie/*drug therapy/pathology
MH  - Urea/analogs & derivatives/pharmacology/therapeutic use
PMC - PMC3806320
MID - NIHMS476661
COIS- Conflict of interest statement SH Hwang, B. D. Hammock and B. Inceoglu are 
      co-authors on multiple patents filed by the University of California related to 
      soluble epoxide hydrolase inhibitors.
EDAT- 2013/05/09 06:00
MHDA- 2013/08/21 06:00
PMCR- 2014/06/21
CRDT- 2013/05/09 06:00
PHST- 2012/11/15 00:00 [received]
PHST- 2013/04/05 00:00 [revised]
PHST- 2013/04/27 00:00 [accepted]
PHST- 2013/05/09 06:00 [entrez]
PHST- 2013/05/09 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
PHST- 2014/06/21 00:00 [pmc-release]
AID - S0024-3205(13)00239-7 [pii]
AID - 10.1016/j.lfs.2013.04.014 [doi]
PST - ppublish
SO  - Life Sci. 2013 Jun 21;92(23):1145-50. doi: 10.1016/j.lfs.2013.04.014. Epub 2013 
      May 5.