Linked Life Data

20153342

Source:http://linkedlifedata.com/resource/pubmed/id/20153342

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-4-5
pubmed:abstractText
Donepezil is a reversible and noncompetitive cholinesterase inhibitor. The drug is considered as a first-line treatment in patients with mild to moderate Alzheimer's disease. Recently, anti-inflammatory and neuroprotective effects of the drug have been reported. "Cholinergic anti-inflammation pathway" has major implications in these effects. Here, we present evidence that donepezil at 5-20 microM directly acts on microglial cells to inhibit their inflammatory activation. Our conclusion is based on the measurement of nitric oxide and proinflammatory mediators using purified microglia cultures and microglia cell lines: donepezil attenuated microglial production of nitric oxide and tumor necrosis factor (TNF)-alpha, and suppressed the gene expression of inducible nitric oxide synthase, interleukin-1 beta, and TNF-alpha. Subsequent studies showed that donepezil inhibited a canonical inflammatory NF-kappaB signaling. Microglia/neuroblastoma coculture and animal experiments supported the anti-inflammatory effects of donepezil. Based on the studies using nicotinic acetylcholine receptor antagonists, the donepezil inhibition of microglial activation was independent of acetylcholine and its receptor. Thus, inflammatory activation signaling of microglia may be one of the direct targets of donepezil in the central nervous system. It should be noted, however, that there is a large gap between the therapeutic dose of the drug used clinically and the concentration of the drug that exerts the direct action on microglial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-7064
pubmed:author
pubmed:copyrightInfo
(c) 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1122-9
pubmed:meshHeading
pubmed-meshheading:20153342-Animals, pubmed-meshheading:20153342-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:20153342-Cell Line, pubmed-meshheading:20153342-Cell Line, Tumor, pubmed-meshheading:20153342-Cells, Cultured, pubmed-meshheading:20153342-Coculture Techniques, pubmed-meshheading:20153342-Disease Models, Animal, pubmed-meshheading:20153342-Encephalitis, pubmed-meshheading:20153342-Gene Expression, pubmed-meshheading:20153342-Indans, pubmed-meshheading:20153342-Interleukin-1beta, pubmed-meshheading:20153342-Mice, pubmed-meshheading:20153342-Microglia, pubmed-meshheading:20153342-NF-kappa B, pubmed-meshheading:20153342-Neuroimmunomodulation, pubmed-meshheading:20153342-Nitric Oxide, pubmed-meshheading:20153342-Nitric Oxide Synthase Type II, pubmed-meshheading:20153342-Piperidines, pubmed-meshheading:20153342-Rats, pubmed-meshheading:20153342-Signal Transduction, pubmed-meshheading:20153342-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
Microglia signaling as a target of donepezil.
pubmed:affiliation
Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, 101 Dong-In, Joong-gu, Daegu 700-422, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't