Linked Life Data

12183682

Source:http://linkedlifedata.com/resource/pubmed/id/12183682

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-8-16
pubmed:abstractText
Previously we reported that naloxone stereoisomers, in an opioid receptor-independent manner, attenuated the inflammation-mediated degeneration of dopaminergic neurons by inhibition of the activation of microglia, the resident immune cells in the brain. Recently we discovered that beta-amyloid peptide Abeta (1-42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic neurons through the activation of microglia and production of superoxide. The purpose of this study was to determine whether naloxone isomers had any effect on Abeta (1-42)-induced neurodegeneration. Pretreatment of either cortical or mesencephalic neuron-glia cultures with 1 to 10 microM (-)-naloxone, prior to treatment for up to 11 days with 0.1 to 3 microM Abeta (1-42), afforded significant neuroprotection as judged by neurotransmitter uptake, immunocytochemical analysis, and cell counting. More importantly, (+)-naloxone, the ineffective enantiomer of (-)-naloxone in binding opioid receptors, was equally effective in affording neuroprotection. Mechanistically, inhibition of Abeta (1-42)-induced production of superoxide in microglia underlay the neuroprotective effect of naloxone stereoisomers. Moreover, neuroprotection and inhibition of Abeta (1-42)-induced superoxide production was also achieved with naloxone methiodide, a charged analog with quaternary amine, suggesting that the site of action for naloxone isomers is at the cell surface of microglia. These results demonstrated that naloxone isomers, through mechanisms unrelated to the opioid receptors, were capable of inhibiting Abeta (1-42)-induced microglial activation and degeneration of both cortical and mesencephalic neurons. Combined with our previous observations with inflammagen-induced neurodegeneration, naloxone analogs, especially (+)-naloxone, may have potential therapeutic efficacy for the treatment of Alzheimer's and Parkinson's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
302
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1212-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12183682-Amyloid beta-Peptides, pubmed-meshheading:12183682-Animals, pubmed-meshheading:12183682-Cells, Cultured, pubmed-meshheading:12183682-Cerebral Cortex, pubmed-meshheading:12183682-Dopamine, pubmed-meshheading:12183682-Immunohistochemistry, pubmed-meshheading:12183682-Male, pubmed-meshheading:12183682-Mesencephalon, pubmed-meshheading:12183682-Microglia, pubmed-meshheading:12183682-Naloxone, pubmed-meshheading:12183682-Narcotic Antagonists, pubmed-meshheading:12183682-Nerve Degeneration, pubmed-meshheading:12183682-Neurons, pubmed-meshheading:12183682-Peptide Fragments, pubmed-meshheading:12183682-Rats, pubmed-meshheading:12183682-Rats, Inbred F344, pubmed-meshheading:12183682-Stereoisomerism, pubmed-meshheading:12183682-Superoxides, pubmed-meshheading:12183682-Tyrosine 3-Monooxygenase, pubmed-meshheading:12183682-gamma-Aminobutyric Acid
pubmed:year
2002
pubmed:articleTitle
Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons.
pubmed:affiliation
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA. liu3@niehs.nih.gov
pubmed:publicationType
Journal Article