Artemether Activation of AMPKGSK3β(ser9)Nrf2 Signaling Confers Neuroprotection towards β-Amyloid-Induced Neurotoxicity in 3xTg Alzheimer’s Mouse Model
Joint Authors
Zheng, Wenhua
Li, Shuai
Zhao, Xia
Lazarovici, Philip
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-24, 24 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-21
Country of Publication
Egypt
No. of Pages
24
Main Subjects
Abstract EN
Alzheimer’s disease is a severe neurodegenerative disease.
Multiple factors involving neurofibrillary tangles and amyloid-β plaques lead to the progression of the AD, generated by aggregated hyperphosphorylated Tau protein.
Inflammation, mitochondrial dysfunction, and oxidative stress play a significant role in the progression of AD.
It has been therefore suggested that the multifactorial nature of AD pathogenesis requires the design of antioxidant drugs with a broad spectrum of neuroprotective activities.
For this reason, the use of natural products, characterized by multiple pharmacological properties is advantageous as AD-modifying drugs over the single-targeted chemicals.
Artemether, a peroxide sesquiterpenoid lipid-soluble compound, has been used in the clinic as an antimalarial drug.
Also, it exhibits potent anti-inflammatory and antioxidant activities.
Here, we report the neuroprotective effects of Artemether towards Aβ-induced neurotoxicity in neuronal cell cultures.
A temporal correlation was found between Artemether neuroprotection towards Aβ-induced neurotoxicity and AMPK/GSK3β phosphorylation activity and increased expression of the activated Nrf2 signaling pathway.
In 3xTg-AD mice, Artemether attenuated learning and memory deficits, inhibited cortical neuronal apoptosis and glial activation, inhibited oxidative stress through decrease of lipid peroxidation and increased expression of SOD, and reduced Aβ deposition and tau protein phosphorylation.
Moreover, in 3xTg-AD mice, Artemether induced phosphorylation of the AMPK/GSK3β pathway which activated Nrf2, increasing the level of antioxidant protein HO-1.
These activities probably produced the antioxidant and anti-inflammatory effects responsible for the neuroprotective effects of Artemether in the 3xTg-AD mouse model.
These findings propose Artemether as a new drug for the treatment of AD disease.
American Psychological Association (APA)
Li, Shuai& Zhao, Xia& Lazarovici, Philip& Zheng, Wenhua. 2019. Artemether Activation of AMPKGSK3β(ser9)Nrf2 Signaling Confers Neuroprotection towards β-Amyloid-Induced Neurotoxicity in 3xTg Alzheimer’s Mouse Model. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-24.
https://search.emarefa.net/detail/BIM-1202392
Modern Language Association (MLA)
Li, Shuai…[et al.]. Artemether Activation of AMPKGSK3β(ser9)Nrf2 Signaling Confers Neuroprotection towards β-Amyloid-Induced Neurotoxicity in 3xTg Alzheimer’s Mouse Model. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-24.
https://search.emarefa.net/detail/BIM-1202392
American Medical Association (AMA)
Li, Shuai& Zhao, Xia& Lazarovici, Philip& Zheng, Wenhua. Artemether Activation of AMPKGSK3β(ser9)Nrf2 Signaling Confers Neuroprotection towards β-Amyloid-Induced Neurotoxicity in 3xTg Alzheimer’s Mouse Model. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-24.
https://search.emarefa.net/detail/BIM-1202392
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202392