Melatonin regulates Aß production/clearance balance and Aß neurotoxicity: A potential therapeutic molecule for Alzheimer's disease.
Biomed Pharmacother
; 132: 110887, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33254429
ABSTRACT
Alzheimer's disease (AD) is an age-related neurodegenerative disease with multiple predisposing factors and complicated pathogenesis. Aß peptide is one of the most important pathogenic factors in the etiology of AD. Accumulating evidence indicates that the imbalance of Aß production and Aß clearance in the brain of AD patients leads to Aß deposition and neurotoxic Aß oligomer formation. Melatonin shows a potent neuroprotective effect and can prevent or slow down the progression of AD, supporting the view that melatonin is a potential therapeutic molecule for AD. Melatonin modulates the regulatory network of secretase expression and affects the function of secretase, thereby inhibiting amyloidogenic APP processing and Aß production. Additionally, melatonin ameliorates Aß-induced neurotoxicity and probably promotes Aß clearance through glymphatic-lymphatic drainage, BBB transportation and degradation pathways. In this review, we summarize and discuss the role of melatonin against Aß-dependent AD pathogenesis. We explore the potential cellular and molecular mechanisms of melatonin on Aß production and assembly, Aß clearance, Aß neurotoxicity and circadian cycle disruption. We summarize multiple clinical trials of melatonin treatment in AD patients, showing that melatonin has a promising effect on improving sleep quality and cognitive function. This review aims to stimulate further research on melatonin as a potential therapeutic agent for AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Peptídeos beta-Amiloides
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Doença de Alzheimer
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Sistema Glinfático
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Melatonina
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2020
Tipo de documento:
Article