Linked Life Data

20637185

Source:http://linkedlifedata.com/resource/pubmed/id/20637185

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-8-31
pubmed:abstractText
Increasing evidence indicates that microglial activation plays an important role in the pathogenesis of Alzheimer's disease (AD). In AD, activated microglia may facilitate the clearance of beta-amyloid (Abeta), a neurotoxic component in AD pathogenesis. However, microglial activation comes at the cost of triggering neuro-inflammation, which contributes to cerebral dysfunction. Thus, pharmacological approaches that can achieve a favorable combination of a reduced microglia-mediated neuro-inflammation, and an enhanced Abeta clearance may be beneficial for preventing the progression of the disease. Here, we show that some newly synthesized compounds may exert such a combination of functions. Using mouse primary microglia and RAW264.7 cells, we found that some thiourea derivatives significantly enhanced microglial Abeta phagocytosis and suppressed microglial immune responses, as evidenced by the reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Of note, some commercially available inhibitors for iNOS and/or COX-2, such as ibuprofen, dextromethorphan, and N(G)-methyl-l-arginine (l-NMA), show negligible effects on microglial Abeta phagocytosis. Among the thiourea derivatives, our data show that a lead compound, designated as compound #326, (1-Naphthalen-1-yl-3-[5-(3-thioureido-phenoxy)-pentyl]-thiourea) appears to be the most potent in promoting Abeta phagocytosis and in inhibiting the LPS-induced expression of iNOS and COX-2 (when used at concentrations in the low muM range). The potency of compound #326 may have beneficial effects on modulating microglial activation in AD. The structure-activity relationship indicates that the thiourea group, alkyl linker, and the hydrophobic aryl group largely influence the dual functions of the compounds. These findings may indicate a structural basis for the improved design of future drug therapies for AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1872-7786
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
188
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
228-36
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Modulation of microglial immune responses by a novel thiourea derivative.
pubmed:affiliation
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't