Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

Xian, Yan‐Fang; Qu, Chang; Liu, Yue; Ip, Siu‐Po; Yuan, Qiuju; Yang, Wen; Lin, Zhi‐Xiu

doi:10.1155/2020/5920476

Cited by 26 publications

(17 citation statements)

References 57 publications

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“…Increasing evidence reveals that dysfunction of the PI3K/Akt signaling pathway is closely related to several features of the pathology of AD, including neuroinflammation mediated by gliocyte activation, A β production, and neuron loss [ 35 ]. Previous studies identified therapies that regulate the PI3K/Akt signaling pathway exert cognitive deficits improving effects in experimental models of AD via suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction [ 36 ]. Our examination demonstrated that in the brain tissues of APP/PS1 mice, the activation of glial cells, as assessed by Iba1 and GFAP immunoreactivity, was increased together with the activation of PI3K.…”

Section: Discussionmentioning

confidence: 99%

NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

Zha

Fang

et al. 2020

Oxidative Medicine and Cellular Longevity

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NLRC3 inhibits inflammatory responses. Neuroinflammation induces and accelerates the onset of Alzheimer’s disease (AD). This study is aimed at investigating whether NLRC3 plays a role in neuroinflammation, Aβ accumulation, and neuroprotection in AD mice. 12-month-old APP/PS1 transgenic and C57 mice were used for studies in vivo. In vitro, organotypic hippocampal slices were cultured. We found that the expression of NLRC3 was downregulated in the brain tissues of APP/PS1 mice. Mice in the APP/PS1 group had a significant attenuation of learning and memory ability compared to the control group, and the ability was improved in APP/PS1 + LV-NLRC3 mice. The expressions of 6E10, GFAP, Iba1, and PI3K in the hippocampus and brains of APP/PS1 mice were significantly higher than those of the control group, while the expressions of NeuN were lower than that of the control group. With the overexpression of NLRC3 in the APP/PS1 + LV-NLRC3 group, the expressions of 6e10, GFAP, Iba1, and PI3K were significantly lower, while the expression of NeuN was significantly higher compared to the APP/PS1 group. NLRC3 colocalized with NeuN. PI3K activation with 740YP increased the expression of GFAP and Iba-1 in the hippocampus with the exogenous NLRC3 protein. We conclude that NLRC3 may play an important role in the development and progression of AD. Downregulation of NLRC3 can lead to the activation of PI3K, resulting in abnormal plaque deposition, glial cell activation, and neuron loss during AD. NLRC3 delays the progression of AD in APP/PS1 mice via inhibiting PI3K activation.

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Section: Discussionmentioning

confidence: 99%

NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

Zha

Fang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…( Lawrence 2009 ; Oboudiyat et al, 2013 ; Wang M. et al, 2017 ; Xie et al, 2020 ). Moreover, MN (1) inhibited the activities of β-secretase and γ-secretase and enhanced the Aβ-degrading enzymatic activities via adjusting the PI3K/Akt/GSK-3β pathway ( Aggarwal et al, 2012 ; Xian et al, 2020 ). LXR, the target gene of PPAR-γ, was activated by MN (1) to upregulate other genes including ABCA1 and ApoE which mediated the lysosomal clearance of Aβ, reducing Aβ toxicity ( Cramer et al, 2012 ; Oboudiyat et al, 2013 ; Bonet-Costa et al, 2016 ; Zhang et al, 2018 ; Xie et al, 2020 ).…”

Section: Mechanism Underlying the Effects Of Neolignans In Ndsmentioning

confidence: 99%

“…Besides, MN (1) could inhibit NF-κB activation and IκB degradation in RAW264.7 cells stimulated with lipopolysaccharide ( Fu et al, 2013 ). In addition, Male TgCRND8 mice were orally administered with MN (1) daily for 4 consecutive months, then researchers found that the regulation of NF-κB might be related to activation of PPAR-γ ( Aggarwal et al, 2012 ; Oboudiyat et al, 2013 ; Xian et al, 2020 ; Xie et al, 2020 ). Specifically, the DNA-binding activity of NF-κB was inhibited by PPAR-γ activation.…”

Section: Mechanism Underlying the Effects Of Neolignans In Ndsmentioning

confidence: 99%

Neuroprotective Potency of Neolignans in Magnolia officinalis Cortex Against Brain Disorders

et al. 2022

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In recent years, neurological diseases including Alzheimer’s disease, Parkinson’s disease and stroke are one of the main causes of death in the world. At the same time, the incidence of psychiatric disorders including depression and anxiety has been increasing. Accumulating elderly and stressed people suffer from these brain disorders, which is undoubtedly a huge burden on the modern aging society. Neolignans, the main active ingredients in Magnolia officinalis cortex, were reported to have neuroprotective effects. In addition, the key bioactive ingredients of neolignans, magnolol (1) and honokiol (2), were proved to prevent and treat neurological diseases and psychiatric disorders by protecting nerve cells and brain microvascular endothelial cells (BMECs). Furthermore, neolignans played a role in protecting nerve cells via regulation of neuronal function, suppression of neurotoxicity, etc. This review summarizes the neuroprotective effect, primary mechanisms of the leading neolignans and provides new prospects for the treatment of brain disorders in the future.

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“…Neuromorphological abnormalities do not appear in this mouse model until 6 months of age [ 95 ]. Age-related behavioral impairments in TgCRND8 mice are observed starting at 3 months of age in spatial working and reference memory tasks including the Barnes maze, MWM, NOR, and FC tests [ 93 , 96 , 97 , 98 , 99 , 100 ]. Therefore, this mouse model, as well as Tg2576, could be potentially powerful models for developing therapeutic drugs to treat early-onset AD.…”

Section: Biomarkers and Amyloid Cascade Hypothesis-related Animal Modelsmentioning

confidence: 99%

Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment

Nakai

Yamada

Mizoguchi

2021

IJMS

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Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.

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Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

Cited by 26 publications

References 57 publications

NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

NLRC3 Delays the Progression of AD in APP/PS1 Mice via Inhibiting PI3K Activation

Neuroprotective Potency of Neolignans in Magnolia officinalis Cortex Against Brain Disorders

Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment

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