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The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors.
J Pineal Res. 2002 Apr; 32(3):135-42.JP

Abstract

Exposure of neuronal cells to the Alzheimer's amyloid beta protein (Abeta) results in extensive oxidative damage of bio-molecules that are profoundly harmful to neuronal homeostasis. It has been demonstrated that melatonin protects neurons against Abeta-mediated neurotoxicity, including cell death and a spectrum of oxidative lesions. We undertook the current study to determine whether melatonin membrane receptors are involved in the mechanism of neuroprotection against Abeta neurotoxicity. For this purpose, we characterized the free-radical scavenging potency of several compounds exhibiting various affinities for melatonin membrane receptors (MLT 1a and 1b). Abeta-mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against Abeta toxicity was observed when we used melatonin membrane receptor agonists that were devoid of antioxidant activity. In contrast, the cells were fully protected in parallel control experiments when either melatonin, or the structurally unrelated free-radical scavenger phenyl-N-t-butyl nitrone (PBN), were added to Abeta-containing culture media. This study demonstrates that the neuroprotective properties of melatonin against Abeta-mediated toxicity does not require binding of melatonin to a membrane receptor and is likely the result of the antioxidant and antiamyloidogenic features of the agent.

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Authors+Show Affiliations

Pappolla MA
Department of Pathology, University of South Alabama, Mobile 36617, USA. memorycenter@aol.com
Simovich MJ
No affiliation info available
Bryant-Thomas T
No affiliation info available
Chyan YJ
No affiliation info available
Poeggeler B
No affiliation info available
Dubocovich M
No affiliation info available
Bick R
No affiliation info available
Perry G
No affiliation info available
Cruz-Sanchez F
No affiliation info available
Smith MA
No affiliation info available

MeSH

5-MethoxytryptamineAmyloid beta-PeptidesAnimalsAntioxidantsCells, CulturedCyclic N-OxidesFree Radical ScavengersHippocampusHumansMelatoninNeuroblastomaNeuronsNeuroprotective AgentsNitrogen OxidesRatsReceptors, Cell SurfaceReceptors, Cytoplasmic and NuclearReceptors, MelatoninSerotonin

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12074096

Citation

Pappolla, Miguel A., et al. "The Neuroprotective Activities of Melatonin Against the Alzheimer Beta-protein Are Not Mediated By Melatonin Membrane Receptors." Journal of Pineal Research, vol. 32, no. 3, 2002, pp. 135-42.
Pappolla MA, Simovich MJ, Bryant-Thomas T, et al. The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors. J Pineal Res. 2002;32(3):135-42.
Pappolla, M. A., Simovich, M. J., Bryant-Thomas, T., Chyan, Y. J., Poeggeler, B., Dubocovich, M., Bick, R., Perry, G., Cruz-Sanchez, F., & Smith, M. A. (2002). The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors. Journal of Pineal Research, 32(3), 135-42.
Pappolla MA, et al. The Neuroprotective Activities of Melatonin Against the Alzheimer Beta-protein Are Not Mediated By Melatonin Membrane Receptors. J Pineal Res. 2002;32(3):135-42. PubMed PMID: 12074096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors. AU - Pappolla,Miguel A, AU - Simovich,Marcia J, AU - Bryant-Thomas,Tara, AU - Chyan,Yau-Jan, AU - Poeggeler,Burkhard, AU - Dubocovich,Margarita, AU - Bick,Roger, AU - Perry,George, AU - Cruz-Sanchez,Felix, AU - Smith,Mark A, PY - 2002/6/21/pubmed PY - 2002/11/26/medline PY - 2002/6/21/entrez SP - 135 EP - 42 JF - Journal of pineal research JO - J Pineal Res VL - 32 IS - 3 N2 - Exposure of neuronal cells to the Alzheimer's amyloid beta protein (Abeta) results in extensive oxidative damage of bio-molecules that are profoundly harmful to neuronal homeostasis. It has been demonstrated that melatonin protects neurons against Abeta-mediated neurotoxicity, including cell death and a spectrum of oxidative lesions. We undertook the current study to determine whether melatonin membrane receptors are involved in the mechanism of neuroprotection against Abeta neurotoxicity. For this purpose, we characterized the free-radical scavenging potency of several compounds exhibiting various affinities for melatonin membrane receptors (MLT 1a and 1b). Abeta-mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against Abeta toxicity was observed when we used melatonin membrane receptor agonists that were devoid of antioxidant activity. In contrast, the cells were fully protected in parallel control experiments when either melatonin, or the structurally unrelated free-radical scavenger phenyl-N-t-butyl nitrone (PBN), were added to Abeta-containing culture media. This study demonstrates that the neuroprotective properties of melatonin against Abeta-mediated toxicity does not require binding of melatonin to a membrane receptor and is likely the result of the antioxidant and antiamyloidogenic features of the agent. SN - 0742-3098 UR - https://www.unboundmedicine.com/medline/citation/12074096/The_neuroprotective_activities_of_melatonin_against_the_Alzheimer_beta_protein_are_not_mediated_by_melatonin_membrane_receptors_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0742-3098&date=2002&volume=32&issue=3&spage=135 DB - PRIME DP - Unbound Medicine ER -