Genipin Attenuates Tau Phosphorylation and Aß Levels in Cellular Models of Alzheimer's Disease.
Mol Neurobiol
; 58(8): 4134-4144, 2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-33948899
ABSTRACT
Alzheimer's disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aß) production or removing these molecules is considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. In this study, the effect and molecular mechanisms of genipin on the inhibition of Tau aggregation and Aß generation were investigated. The results showed that genipin bound to Tau and protected against heparin-induced Tau fibril formation. Moreover, genipin suppressed Tau phosphorylation probably by downregulating the expression of CDK5 and GSK-3ß, and activated mTOR-dependent autophagy via the SIRT1/LKB1/AMPK signaling pathway in Tau-overexpressing cells. In addition, genipin decreased Aß production by inhibiting BACE1 expression through the PERK/eIF2α signaling pathway in N2a/SweAPP cells. These data indicated that genipin could effectively lead to a significant reduction of phosphorylated Tau level and Aß generation in vitro, suggesting that genipin might be developed into an effective therapeutic complement or a potential nutraceutical for preventing AD.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Proteínas tau
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Iridoides
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article