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Article

Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells

by
Nongnuch Singrang
1,
Chutikorn Nopparat
2,
Jiraporn Panmanee
3 and
Piyarat Govitrapong
1,*
1
Chulabhorn Graduate Institute, Bangkok 10210, Thailand
2
Innovative Learning Center, Srinakharinwirot University, Bangkok 10110, Thailand
3
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(10), 5225; https://doi.org/10.3390/ijms25105225
Submission received: 21 March 2024 / Revised: 2 May 2024 / Accepted: 2 May 2024 / Published: 10 May 2024

Abstract

Stroke and Alzheimer’s disease (AD) are prevalent age-related diseases; however, the relationship between these two diseases remains unclear. In this study, we aimed to investigate the ability of melatonin, a hormone produced by the pineal gland, to alleviate the effects of ischemic stroke leading to AD by observing the pathogenesis of AD hallmarks. We utilized SH-SY5Y cells under the conditions of oxygen–glucose deprivation (OGD) and oxygen-glucose deprivation and reoxygenation (OGD/R) to establish ischemic stroke conditions. We detected that hypoxia-inducible factor-1α (HIF-1α), an indicator of ischemic stroke, was highly upregulated at both the protein and mRNA levels under OGD conditions. Melatonin significantly downregulated both HIF-1α mRNA and protein expression under OGD/R conditions. We detected the upregulation of β-site APP-cleaving enzyme 1 (BACE1) mRNA and protein expression under both OGD and OGD/R conditions, while 10 µM of melatonin attenuated these effects and inhibited beta amyloid (Aβ) production. Furthermore, we demonstrated that OGD/R conditions were able to activate the BACE1 promoter, while melatonin inhibited this effect. The present results indicate that melatonin has a significant impact on preventing the aberrant development of ischemic stroke, which can lead to the development of AD, providing new insight into the prevention of AD and potential stroke treatments.
Keywords: Alzheimer’s disease; beta amyloid; ischemic stroke; oxygen–glucose deprivation and reoxygenation; melatonin; hypoxia-inducible factor-1α Alzheimer’s disease; beta amyloid; ischemic stroke; oxygen–glucose deprivation and reoxygenation; melatonin; hypoxia-inducible factor-1α

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MDPI and ACS Style

Singrang, N.; Nopparat, C.; Panmanee, J.; Govitrapong, P. Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells. Int. J. Mol. Sci. 2024, 25, 5225. https://doi.org/10.3390/ijms25105225

AMA Style

Singrang N, Nopparat C, Panmanee J, Govitrapong P. Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells. International Journal of Molecular Sciences. 2024; 25(10):5225. https://doi.org/10.3390/ijms25105225

Chicago/Turabian Style

Singrang, Nongnuch, Chutikorn Nopparat, Jiraporn Panmanee, and Piyarat Govitrapong. 2024. "Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells" International Journal of Molecular Sciences 25, no. 10: 5225. https://doi.org/10.3390/ijms25105225

APA Style

Singrang, N., Nopparat, C., Panmanee, J., & Govitrapong, P. (2024). Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells. International Journal of Molecular Sciences, 25(10), 5225. https://doi.org/10.3390/ijms25105225

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