The DOI matches its Crossref record; 62 of the 63 references it cites were found in a registry or an index.
Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide
Open accessAbstract
Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca2+ increases induced by a cytotoxic fragment of Abeta. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.
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“Studies have also reported that antioxidants protect against Aβ induced neuronal toxicity [16,17].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [17]
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Research works printed but not linked: 1
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Зайнуллин, В. Г., & Moskalev, A. (2001) · Russian Journal of Developmental Biology · doi:10.1023/a:1016766516285 · Cited by 7
“Melatonin increases the expression of Mg-, Cu-, Zn-dependent superoxide dismutase in the nervous tissue, thus protecting the neurons against apoptosis mediated by active oxygen forms and calcium accumulation (Anisimov, 1997; Pappola et al. , 1997).”
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“Using murine neuroblastoma cells (N2a), Pappola et al, 1997 [37, 38] first demonstrated that co-incubation of neuroblastoma cells with amyloid-β polypeptide and melatonin significantly reduced several features of apoptosis, including cellular shrinkage and formation of membrane blebs.”
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Muñoz, F. J., Solé, M., & Coma, M. (2006) · Springer eBooks · doi:10.1007/0-387-23226-5_7 · Cited by 7
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“When neuroblastoma cells were incubated with Aβ, more than 80% of the neurons died due to apoptosis, but the presence of melatonin reduced cellular death and DNA damage in a dose-dependent manner [178].”
BackgroundMelatonin in Health and Disease
Fitzpatrick, A. J. (2006) · Alternative and Complementary Therapies · doi:10.1089/act.2006.12.282 · Cited by 4
“124 Recent in vitro 125–127 and animal 128 findings have indicated that melatonin, as an antioxidant, produced pronounced neuroprotective effects against (cid:96) -amyloid peptide, one of the specific underlying causes of Alzheimer’s disease.”
Kim, J. H., Choi, J. M., Lee, S., & Cho, E. J. (2012) · Journal of Agricultural Science · doi:10.5539/jas.v4n4p223 · Cited by 4
“Many studies suggest the possible therapeutic uses of free radical scavengers and antioxidants in the treatment of AD pathogenesis (Pappolla et al., 1997; Bruce et al., 1996).”
BackgroundMelatonin, Neurogenesis, and Aging Brain
López, L. C., Escames, G., López, A., Garcia, J., Doerrier, C., & Acuña-Castroviejo, D. (2010) · The Open Neuroendocrinology Journal · Cited by 4
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Moskalev, A., Krementsova, A. V., & Малышева, О. А. (2008) · Ecological genetics · doi:10.17816/ecogen6324-32 · Cited by 4
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Dzhambazova, T., Kondakova, V., Tsvetkov, I., & Batchvarov, R. (2011) · InTech eBooks · doi:10.5772/29800 · Cited by 4
“It was found that melatonin prevents death of cultured neuronal cells caused by exposure to ┚APs (Pappolla et al., 1997).”
BackgroundGonos, E. S., Agrafiotis, D., Dontas, A. S., Efthimiopoulos, S., Galaris, D., Karamanos, N. K., Kletsas, D., Kolettas, E., Panayotou, G., Pratsinis, H., et al. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00017-7 · Cited by 4
Chapter 3. β-Amyloid as a Target for Alzheimer's Disease Therapy
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Lee, Y.-H. (2012) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.984 · Cited by 3
“Multiple studies have shown that antioxidants and free radical scavengers inhibit A β -induced neurotoxicity (11-13) and antioxidant substances improve spatial cognition and retard AD pathogenesis (14,15).”
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López, F. J. M. (2001) · Revista Española de Geriatría y Gerontología · doi:10.1016/s0211-139x(01)74694-x · Cited by 2
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Haiwei, X., Fan, X., Gao, E., Wu, X., Cao, J., & Li, H.-D. (2003) · Neuroscience Research Communications · doi:10.1002/nrc.10079 · Cited by 2
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Zhang, H., Hamit, D., Li, Q., Hu, X., Li, S.-F., Xu, F., Wang, M., Bao, G.-Q., & Li, H. (2025) · Scientific Reports · doi:10.1038/s41598-024-80755-x · Cited by 1
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Polimeni, G., Guarneri, C., & Cuzzocrea, S. (2016) · Springer eBooks · doi:10.1007/978-81-322-2803-5_6 · Cited by 1
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Metadata
- Authors
- Pappolla, M. A., Sos, M., Omar, R. A., Bick, R. J., Hickson-Bick, D. L. M., Reiter, R. J., Efthimiopoulos, S., & Robakis, N. K.
- Affiliations
- University of South Alabama (US)
- The University of Texas Health Science Center at Houston (US)
- University of Louisville (US)
- The University of Texas at San Antonio Health Science Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-03-01
- Volume
- 17
- Issue
- 5
- Pages
- 1683-1690
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573387
- OpenAlex
- W2137034584
- Cited by
- 359
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 12 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 16 · 2013: 15 · 2012: 14
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag011130-03)
- National Institute on Aging (RF1AG008200, R56AG008200, AG-08200, AG-11130, R01AG008200)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- melatonin, Alzheimer's disease, amyloid-beta, neuroblastoma cells, oxidative stress, neurotoxicity, cell death, intracellular calcium, aging, pineal hormone
- MeSH terms
- Alzheimer Disease, Animals, Antioxidants, Calcium, Ditiocarb, Doxorubicin, Melatonin, Neuroblastoma, Neurons, Peptide Fragments, Peptides, Superoxide Dismutase, Reproducibility of Results, Lipid Peroxidation, Amyloid beta-Peptides, PC12 Cells, Apoptosis, Oxidative Stress, Mice, Rats
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