Melatonin Attenuates Methamphetamine-Induced Alteration of Amyloid β Precursor Protein Cleaving Enzyme Expressions via Melatonin Receptor in Human Neuroblastoma Cells
Issued Date
2022-08-01
Resource Type
ISSN
10298428
eISSN
14763524
Scopus ID
2-s2.0-85131318430
Pubmed ID
35648367
Journal Title
Neurotoxicity Research
Volume
40
Issue
4
Start Page
1086
End Page
1095
Rights Holder(s)
SCOPUS
Bibliographic Citation
Neurotoxicity Research Vol.40 No.4 (2022) , 1086-1095
Suggested Citation
Nopparat C., Boontor A., Panmanee J., Govitrapong P. Melatonin Attenuates Methamphetamine-Induced Alteration of Amyloid β Precursor Protein Cleaving Enzyme Expressions via Melatonin Receptor in Human Neuroblastoma Cells. Neurotoxicity Research Vol.40 No.4 (2022) , 1086-1095. 1095. doi:10.1007/s12640-022-00522-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86841
Title
Melatonin Attenuates Methamphetamine-Induced Alteration of Amyloid β Precursor Protein Cleaving Enzyme Expressions via Melatonin Receptor in Human Neuroblastoma Cells
Author(s)
Other Contributor(s)
Abstract
Alzheimer’s disease (AD) is the most prominent neurodegenerative disease represented by the loss of memory and cognitive impairment symptoms and is one of the major health imperilments among the elderly. Amyloid (Aβ) deposit inside the neuron is one of the characteristic pathological hallmarks of this disease, leading to neuronal cell death. In the amyloidogenic processing, the amyloid precursor protein (APP) is cleaved by beta-secretase and γ-secretase to generate Aβ. Methamphetamine (METH) is a psychostimulant drug that causes neurodegeneration and detrimental cognitive deficits. The analogy between the neurotoxic and neurodegenerative profile of METH and AD pathology necessitates an exploration of the underlying molecular mechanisms. In the present study, we found that METH ineluctably affects APP processing, which might contribute to the marked production of Aβ in human neuroblastoma cells. Melatonin, an indolamine produced and released by the pineal gland as well as other extrapineal, has been protective against METH-induced neurodegenerative processes, thus rescuing neuronal cell death. However, the precise action of melatonin on METH has yet to be determined. We further propose to investigate the protective properties of melatonin on METH-induced APP-cleaving secretases. Pretreatment with melatonin significantly reversed METH-induced APP-cleaving secretases and Aβ production. In addition, pretreatment with luzindole, a melatonin receptor antagonist, significantly prevented the protective effect of melatonin, suggesting that the attenuation of the toxic effect on METH-induced APP processing by melatonin was mediated via melatonin receptor. The present results suggested that melatonin has a beneficial role in preventing Aβ generation in a cellular model of METH-induced AD.