The neuroprotective activities of melatonin against the Alzheimer β-protein are not mediated by melatonin membrane receptors

Miguel Pappolla, Marcia J. Simovich, Tara Bryant-Thomas, Yau Jan Chyan, Burkhard Poeggeler, Margarita Dubocovich, Roger Bick, George Perry, Felix Cruz-Sanchez, Mark A. Smith

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Exposure of neuronal cells to the Alzheimer's amyloid β protein (Aβ) resuhs in extensive oxidative damage of bio-molecules that are profoundly harmful to neuronal homeostasis. It bas been demonstrated that melatonin protects neurons against Aβ-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 Aβ 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), Aβ-mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against Aβ 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 Aβ-containing culture media. This study demonstrates that the neuroprotective properties of melatonin against Aβ-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.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalJournal of Pineal Research
Volume32
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

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Melatonin Receptors
Melatonin
Membranes
Proteins
Antioxidants
Neurons
Serum Amyloid A Protein
Free Radical Scavengers
Neuroblastoma
Free Radicals
Culture Media
Homeostasis
Cell Death

ASJC Scopus subject areas

  • Endocrinology

Cite this

The neuroprotective activities of melatonin against the Alzheimer β-protein are not mediated by melatonin membrane receptors. / Pappolla, Miguel; Simovich, Marcia J.; Bryant-Thomas, Tara; Chyan, Yau Jan; Poeggeler, Burkhard; Dubocovich, Margarita; Bick, Roger; Perry, George; Cruz-Sanchez, Felix; Smith, Mark A.

In: Journal of Pineal Research, Vol. 32, No. 3, 2002, p. 135-142.

Research output: Contribution to journalArticle

Pappolla, M, Simovich, MJ, Bryant-Thomas, T, Chyan, YJ, Poeggeler, B, Dubocovich, M, Bick, R, Perry, G, Cruz-Sanchez, F & Smith, MA 2002, 'The neuroprotective activities of melatonin against the Alzheimer β-protein are not mediated by melatonin membrane receptors', Journal of Pineal Research, vol. 32, no. 3, pp. 135-142. https://doi.org/10.1034/j.1600-079x.2002.1o838.x
Pappolla, Miguel ; Simovich, Marcia J. ; Bryant-Thomas, Tara ; Chyan, Yau Jan ; Poeggeler, Burkhard ; Dubocovich, Margarita ; Bick, Roger ; Perry, George ; Cruz-Sanchez, Felix ; Smith, Mark A. / The neuroprotective activities of melatonin against the Alzheimer β-protein are not mediated by melatonin membrane receptors. In: Journal of Pineal Research. 2002 ; Vol. 32, No. 3. pp. 135-142.
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