Artemether Attenuates Aß25-35-Induced Cognitive Impairments by Downregulating Aß, BACE1, mTOR and Tau Proteins.
Clin Lab
; 67(10)2021 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-34655202
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment.METHODS:
The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model.RESULTS:
Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells.CONCLUSIONS:
The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Disfunção Cognitiva
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article