Add like
Add dislike
Add to saved papers

Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons.

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.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

Managing Alcohol Withdrawal Syndrome.Annals of Emergency Medicine 2024 March 26

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app