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The neuroprotective activities of melatonin against the Alzheimer β‐protein are not mediated by melatonin membrane receptors
Author(s) -
Pappolla Miguel A.,
Simovich Marcia J.,
BryantThomas Tara,
Chyan YauJan,
Poeggeler Burkhard,
Dubocovich Margarita,
Bick Roger,
Perry George,
CruzSanchez Felix,
Smith Mark A.
Publication year - 2002
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2002.1o838.x
Subject(s) - melatonin , neurotoxicity , neuroprotection , melatonin receptor , free radical scavenger , pharmacology , receptor , chemistry , antioxidant , toxicity , biology , biochemistry , endocrinology , organic chemistry
Exposure of neuronal cells to the Alzheimer's amyloid β protein (A β ) results in extensive oxidative damage of bio‐molecules that are profoundly harmful to neuronal homeostasis. It has been demonstrated that melatonin protects neurons against A β ‐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 A β 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). A β ‐mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against A β 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 A β ‐containing culture media. This study demonstrates that the neuroprotective properties of melatonin against A β ‐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.