Artemether Attenuates Aβ25-35-Induced Cognitive Impairments by Downregulating Aβ, BACE1, mTOR and Tau Proteins
| Autor: | Zhen-Zhen Xue, Chun Hou, Hong-Juan Li, Hong-Yu Liu, Qi-Shun Zhu, Cheng-Wei Gao, Li Cong, Yan Chen, Dong-Mei Chen, Ji-Lin Yang, Qian Yao, Qiu-Chen Cai, Tian-Zuo Wang, Yin Zhang, Chuan-hai Cao |
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| Rok vydání: | 2021 |
| Předmět: |
Amyloid beta
tau Proteins Pharmacology Blood–brain barrier medicine.disease_cause General Biochemistry Genetics and Molecular Biology In vivo Alzheimer Disease medicine Animals Aspartic Acid Endopeptidases Cognitive Dysfunction Senile plaques Artemether PI3K/AKT/mTOR pathway Neuroinflammation Amyloid beta-Peptides biology business.industry TOR Serine-Threonine Kinases Peptide Fragments Rats medicine.anatomical_structure biology.protein Amyloid Precursor Protein Secretases business Oxidative stress medicine.drug |
| Zdroj: | Clinical laboratory. 67(10) |
| ISSN: | 1433-6510 |
| Popis: | 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 (Aβ) induced neural apoptosis. Moreover, overexpression of β-secretase 1 (BACE1), Aβ, 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 Aβ25-35 induced cognitive impairments rat model. RESULTS Results of the in vivo study showed that oral administration of artemether significantly attenuated Aβ25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aβ, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS The beneficial effect of artemether against Aβ 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aβ, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment. |
| Databáze: | OpenAIRE |
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