Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Yadong ZhaiXiaobo Sun

Abstract

Diabetes is associated with a high risk of developing cognitive dysfunction and neuropsychiatric disabilities, and these disease symptomsare termed diabetic encephalopathy (DEP). Inflammation is involved in the development of DEP. The cleavage and maturation of the proinflammatory cytokine interleukin (IL)-1β is regulated by the NLRP3 inflammasome. Obese and type 2 diabetic db/db mice show anxiety- and depression-like behaviors and cognitive disorders associated with hippocampal inflammation. The purpose of this study was to explore the role of NLRP3 inflammasome in DEP. Results showed that expression levels of inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1, as well as IL-1β in the hippocampus of diabetic db/db mice were higher than those of non-diabetic db/m mice. Treatment of db/db mice with NLRP3 inflammasome inhibitor MCC950 ameliorated anxiety- and depression-like behaviors as well as cognitive dysfunction, and reversed increased NLRP3, ASC, and IL-1βexpression levels and caspase-1 activity in hippocampus. Moreover, MCC950 treatment significantly improved insulin sensitivity in db/db mice. These results demonstrate that inhibition of NLRP3 inflammasome activation may p...Continue Reading

References

May 19, 2004·Archives of Neurology·Zoe ArvanitakisDavid A Bennett
Apr 7, 2006·Diabetologia·G S MijnhoutR J Heine
Jul 20, 2010·Physiology & Behavior·Ajaykumar N SharmaJames B Lucot
Jan 11, 2011·Nature Medicine·Bolormaa VandanmagsarVishwa Deep Dixit
Jun 12, 2012·Lancet·Rory J McCrimmonBrian M Frier
Jul 31, 2014·Kidney International·Khurrum ShahzadBerend Isermann
Jan 22, 2015·The International Journal of Neuropsychopharmacology·Yi ZhangChun-Lei Jiang
Jun 11, 2015·International Journal of Endocrinology·S W SetoD Chang
Aug 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Changyun HuLi Wen
Oct 9, 2015·Saudi Medical Journal·Essmat M GemeayWafaa O Nadrah
Dec 3, 2015·Journal of Lipid Research·Yongeun KimSoonkyu Chung
Mar 22, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ai-Li CaoWen Peng
Jul 12, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bin ZhangXiaobo Sun
Dec 29, 2016·Brain, Behavior, and Immunity·Lourdes Fernández de CossíoNathalie Castanon
Feb 17, 2017·Biochemical and Biophysical Research Communications·Xinchun YeGuiyun Cui

❮ Previous
Next ❯

Citations

Dec 21, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kehong ChenYani He
Dec 28, 2018·Biology of Reproduction·Jonathan FaroNardhy Gomez-Lopez
May 1, 2019·Nature Reviews. Immunology·Karen V SwansonJenny P-Y Ting
Jul 30, 2019·Journal of Cardiovascular Pharmacology·Marina SokolovaPal Aukrust
Sep 2, 2020·Molecular Neurobiology·Lucineia Gainski DanielskiFabricia Petronilho
Sep 21, 2018·Frontiers in Molecular Neuroscience·Bo-Zong ShaoChong Liu
Oct 5, 2019·Journal of Cardiovascular Pharmacology·Marina SokolovaPål Aukrust
Apr 26, 2019·International Journal of Molecular Sciences·Kurt T K GiulianiPedro H F Gois
Apr 8, 2020·Journal of Neuroinflammation·William T O'BrienStuart J McDonald
Oct 8, 2020·Ocular Immunology and Inflammation·Karanvir S Raman, Joanne A Matsubara
Jan 9, 2021·Molecular Neurobiology·Ernest T ChiveroShilpa Buch
Feb 3, 2021·International Journal of Molecular Sciences·Laura UrwanischJutta Horejs-Hoeck
Feb 2, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Karine Paula ReichertMaria Rosa Chitolina Schetinger
Apr 4, 2021·International Journal of Molecular Sciences·Gonzalo JorqueraPaola Llanos
Apr 3, 2021·Frontiers in Cell and Developmental Biology·Shuangyu LvXiaotian Li
May 22, 2021·Immunopharmacology and Immunotoxicology·Ali Saeedi-BoroujeniAli Khodadadi
Dec 15, 2020·Neuroscience Research·Tomofumi Watanabe, Kazuhiro Sakamoto
Aug 13, 2021·Aging Cell·Thassio MesquitaAhmed Ibrahim
Sep 17, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Abdullah Al MamunJian Xiao
Sep 27, 2021·Journal of Internal Medicine·Youngmin A Lee, Scott L Friedman
Jan 4, 2022·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Qing LiuLi-Tao Yi

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
protein assay

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here