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Neuropharmacology ; 125: 408-417, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28822725

RESUMO

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by memory deficits and cognitive decline. Excessive amyloid-ß (Aß) peptide aggregates and forms soluble oligomers and insoluble cerebral amyloid plaques, which is widely thought to be the underlying pathogenic mechanism of AD. Therefore, effective regulation of Aß metabolism is an important aspect of preventing and improving AD. Berberine, which is the main active component of the traditional medicinal herb Coptidis rhizoma, has a positive effect on reducing Aß levels. However, the exact mechanism involved is unclear and requires more investigation. In the present study, we examined the role of berberine in the activation of AMP-activated protein kinase (AMPK) in neuroblastoma cells and primary cultured neurons and sought to characterize the role of AMPK in the metabolism of Aß. The results indicate that berberine reduces Aß generation and decreases the expression of ß-site APP cleaving enzyme-1 (BACE1) via activating AMPK in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a/APP695sw), N2a cells, and primary cultured cortical neurons. Therefore, berberine reduced the accumulation of Aß, which likely contributes to its memory enhancing effect in patients with AD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos beta-Amiloides/metabolismo , Berberina/farmacologia , Fármacos Neuroprotetores/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Berberina/química , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Reação em Cadeia da Polimerase em Tempo Real
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