Bajijiasu Ameliorates β-Amyloid-Triggered Endoplasmic Reticulum Stress and Related Pathologies in an Alzheimer’s Disease Model

Xu, Tingting; Zhang, Yang; He, Jiayang; Luo, Dan; Luo, Yi; Wang, Yijie; Liu, Wei; Wu, Jun; Zhao, Wei; Fang, Jiansong; Guan, Li; Huang, Shun; Wang, Hong; Lin, Li; Zhang, Shijie; Wang, Qi

doi:10.1159/000488414

Cited by 24 publications

(18 citation statements)

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“…The Morris water maze (MWM) test is the classic behavioral experiment which tests the learning and memory ability [32]. The MWM was procured from ZS Dichuang (Beijing, China) having a xeye Aba video tracking system.…”

Section: Morris Water Maze (Mwm)mentioning

confidence: 99%

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Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Zhao¹,

Li²,

Gaur³

et al. 2020

Aging and disease

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The most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloidbeta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.

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Section: Morris Water Maze (Mwm)mentioning

confidence: 99%

“…On each side of the wall of the quadrants distinct colored papers were placed as visual positional hint. The video tracking camera was staged onto the ceiling directly above the center of the pool to monitor subject swimming parameters [32].…”

Section: Morris Water Maze (Mwm)mentioning

confidence: 99%

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Zhao¹,

Li²,

Gaur³

et al. 2020

Aging and disease

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“…In APP/PS1 mice models, oral of bajijiasu improved learning and memory ability. The effects of bajijiasu have protected neurons against apoptosis, elevated the expression of neurotrophic factors, and alleviated endoplasmic reticulum stress [94].…”

Section: Bajijiasumentioning

confidence: 99%

Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

Wuli

Tsai

Chiou

et al. 2020

IJMS

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Alzheimer’s disease (AD) is characterized by extracellular amyloid plaques composed of the β-amyloid peptides and intracellular neurofibrillary tangles and associates with progressive declines in memory and cognition. Several genes play important roles and regulate enzymes that produce a pathological accumulation of β-amyloid in the brain, such as gamma secretase (γ-secretase). Induced pluripotent stem cells from patients with Alzheimer’s disease with different underlying genetic mechanisms may help model different phenotypes of Alzheimer’s disease and facilitate personalized drug screening platforms for the identification of small molecules. We also discuss recent developments by γ-secretase inhibitors and modulators in the treatment of AD. In addition, small-molecule drugs isolated from Chinese herbal medicines have been shown effective in treating Alzheimer’s disease. We propose a mechanism of small-molecule drugs in treating Alzheimer’s disease. Combining therapy with different small-molecule drugs may increase the chance of symptomatic treatment. A customized strategy tailored to individuals and in combination with therapy may be a more suitable treatment option for Alzheimer’s disease in the future.

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“…Although RP is genetically heterogeneous, apoptosis is widely recognized as the general final pathway for the death of photoreceptors [12]. ERS, caused by excessive misfolded proteins in the ER, could activate the ER unfolded protein response (UPR) and the apoptotic pathways [13–15], which has been associated with neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease [16, 17]. These diseases cause the accumulation of misfolded proteins and ERS, which could eventually lead to the apoptosis of neuronal cells [18].…”

Section: Introductionmentioning

confidence: 99%

Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6b^rd10 Mouse Model of Retinitis Pigmentosa

Yan

Beight

2018

BioMed Research International

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Purpose Lutein, RR-zeaxanthin, and RS-zeaxanthin (L-Z) are antioxidants which can reduce endoplasmic reticulum stress (ERS) and oxidative stress (OS), and ameliorate neurodegenerative diseases. However, their treatment effect in the Pde6brd10 (rd10) mouse model of retinitis pigmentosa (RP) and the underlying cellular mechanisms have not been studied. ERS is an important factor which causes photoreceptor apoptosis. The aim of the current project is to test the treatment effect of L-Z in rd10 mice and to investigate the underlying molecular mechanisms of ERS. Methods L-Z (Lutemax 2020, 10 mg/kg) diluted in sunflower oil (SFO, 1 mg/ml) or the same volume of SFO was administrated via gavage from postnatal day 6 (P6) to P20 daily in L-Z group (n=5) or SFO group (n=6) of rd10 mice. At P21, electroretinography (ERG) was performed to show the functional change of retinas. 78 kDa glucose-regulated protein (GRP78) and endoplasmic reticulum protein 29 (ERp29) were tested by western blot and immunostaining. Results The ERG amplitudes were larger in the L-Z group than those of the SFO group in all flash luminances of dark-adapted and light-adapted ERG (all p < 0.01). Western blot revealed that GRP78 in the retinas of the L-Z group was significantly downregulated compared to that of the SFO group (p < 0.01). Meanwhile, the retinal ERp29 protein was significantly upregulated in the L-Z treatment group than that of the SFO group (p < 0.01). Conclusions L-Z provide protection to the photoreceptors of rd10 mouse model of RP, which is probably associated with the reduction of ERS.

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Bajijiasu Ameliorates β-Amyloid-Triggered Endoplasmic Reticulum Stress and Related Pathologies in an Alzheimer’s Disease Model

Cited by 24 publications

References 60 publications

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6b^rd10 Mouse Model of Retinitis Pigmentosa

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Bajijiasu Ameliorates β-Amyloid-Triggered Endoplasmic Reticulum Stress and Related Pathologies in an Alzheimer’s Disease Model

Cited by 24 publications

References 60 publications

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6brd10 Mouse Model of Retinitis Pigmentosa

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Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in the Pde6b^rd10 Mouse Model of Retinitis Pigmentosa