K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway.

Journal of Neuroinflammation
Hyeon Joo HamJin Tae Hong

Abstract

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111), the inhibitor of CHI3L1, has the inhibitory effect on memory impairment in Αβ infusion mouse model and on LPS-induced neuroinflammation in the murine BV-2 microglia and primary cultured astrocyte. In the present study, we investigated the inhibitory effect of K284-6111 on memory dysfunction and neuroinflammation in Tg2576 transgenic mice, and a more detailed correlation of CHI3L1 and AD. To investigate the effects of K284-6111 on memory dysfunction, we administered K284-6111 (3 mg/kg, p.o.) daily for 4 weeks to Tg2576 mice, followed by behavioral tests of water maze test, probe test, and passive avoidance test. Administration of K284-6111 alleviated memory impairment in Tg2576 mice and had the effect of reducing the accumulation of Aβ and neuroinflammatory responses in the mouse brain. K284-6111 treatment also selectively inactivated ERK and NF-κB pathways, which were activated when CHI3L1 was overexpressed, ...Continue Reading

References

May 1, 1984·Journal of Neuroscience Methods·R Morris
Dec 22, 1999·Clinical and Experimental Immunology·M M LuchettiA Gabrielli
Jan 5, 2001·Expert Opinion on Investigational Drugs·M K O'Banion
Nov 2, 2005·The Journal of Experimental Medicine·Carl NathanM Flint Beal
May 18, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rodrigo MedeirosJoão B Calixto
Nov 13, 2008·Critical Reviews in Clinical Laboratory Sciences·Frederick D Coffman
Nov 13, 2009·World Journal of Gastroenterology : WJG·Katrin EurichEmiko Mizoguchi
Jun 15, 2010·Journal of Neuroinflammation·Dafna Bonneh-BarkayClayton A Wiley
Feb 19, 2011·The International Journal of Neuropsychopharmacology·Chia-Hsiung ChenWeihong Song
Aug 26, 2011·International Journal of Cancer. Journal International Du Cancer·Stephania LibrerosVijaya Iragavarapu-Charyulu
Dec 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hao TangBing Li
Aug 28, 2013·Heart and Vessels·Takeshi SoekiMasataka Sata
Nov 14, 2013·Immunologic Research·Stephania LibrerosVijaya Iragavarapu-Charyulu
Jan 20, 2015·Molecular Neurobiology·Yu Tang, Weidong Le
Apr 19, 2015·Journal of Neuroinflammation·Amir NazemYousef Al-Abed
Jun 27, 2015·Journal of Neuroinflammation·Sun Mi GuJin Tae Hong
Dec 9, 2015·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Jingbo ZhangAbdelilah S Gounni
Apr 26, 2016·Cancer Research Frontiers·Renuka SubramaniamEmiko Mizoguchi
May 18, 2016·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Michelino Di Rosa, Lucia Malaguarnera
Jul 22, 2016·Current Allergy and Asthma Reports·Daniel Elieh Ali KomiAnton Pieter Bussink
Jul 28, 2016·Nature Neuroscience·Richard M Ransohoff
Feb 12, 2017·Current Neuropharmacology·Paweł MuszyńskiBarbara Mroczko
Mar 12, 2017·Current Neurology and Neuroscience Reports·Martin Schain, William Charles Kreisl
Mar 21, 2017·Current Alzheimer Research·Catarina DominguesAna Gabriela Henriques
Apr 4, 2017·Nature Communications·Annalisa NobiliMarcello D'Amelio
Jun 11, 2017·Journal of Neuroinflammation·Marta Querol-VilasecaAlberto Lleó
Jul 1, 2017·Journal of Immunology Research·Joanna SalomonJacek C Szepietowski
Sep 2, 2017·The Journal of Clinical Investigation·Heela Sarlus, Michael T Heneka
Sep 22, 2017·Mediators of Inflammation·Joanna SalomonJacek C Szepietowski
Oct 11, 2017·Molecular and Cellular Neurosciences·C SanfilippoM Di Rosa
Nov 9, 2017·Drugs & Aging·Rita KhouryGeorge T Grossberg

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
ELISA
PCR
transfection
nitric oxide
transgenic

Software Mentioned

GraphPad
Image J
CS
String
LD
GraphPad Prism
SMART

Related Concepts

Related Feeds

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.