GABAB Receptor-Mediated PI3K/Akt Signaling Pathway Alleviates Oxidative Stress and Neuronal Cell Injury in a Rat Model of Alzheimer’s Disease

Sun, Zhanfang; Sun, Lei; Tu, Lixiang

doi:10.3233/jad-191032

Cited by 39 publications

(21 citation statements)

References 38 publications

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“…Aging is one of the most important factors involved in the gradual functional decline and structural degeneration of the brain and has been implicated in memory impairment, which is a major symptom of Alzheimer's disease (AD) [1][2][3]. Due to the rapid aging of the population, memory impairment seriously affects the quality of life of a large number of elderly individuals [4,5].…”

Section: Introductionmentioning

confidence: 99%

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats

Wang

Guo

et al. 2021

BioMed Research International

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Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC-MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3-hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.

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Section: Introductionmentioning

confidence: 99%

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats

Wang

Guo

et al. 2021

BioMed Research International

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“…Decreased levels of PI3K subunits, as well as blunted AKT kinase phosphorylation, have been observed in the brain of AD patients ( Gabbouj et al, 2019 ). Insulin-like growth factor-2 (IGF-2) was reported to attenuate memory decline and amyloid plaque formation in AD mouse model by activating the PI3K/AKT/CREB signaling pathway ( Xia et al, 2019 ), and insulin has been observed to promote neuron growth and synapse formation through the PI3K signaling pathway ( Liem et al, 2017 ; Gabbouj et al, 2019 ). Therefore, we speculate that SV2A may play a role in promoting insulin growth factor secretion.…”

Section: Discussionmentioning

confidence: 99%

The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment

Kong

Huang

et al. 2021

Front. Cell Dev. Biol.

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Alzheimer’s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.

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“…This journal is © The Royal Society of Chemistry 2022 the PI3K-AKT signaling pathway is able to inhibit apoptosis and oxidative stress, thereby protecting neurons against Aβ-induced neurotoxicity and improving learning and memory abilities. 44,45 A compound-target-pathway (C-T-P) network was established to further investigate the interaction of BBB-permeated saponins ( pink nodes), targets of saponins action (blue nodes), and the top 30 pathways ( purple nodes) (see Fig. 7).…”

Section: Food and Function Papermentioning

confidence: 99%

Memory enhancement effect of saponins from Eleutherococcus senticosus leaves and blood–brain barrier-permeated saponins profiling using a pseudotargeted monitoring strategy

Yuhong

Ding

et al. 2022

Food Funct.

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GABAB Receptor-Mediated PI3K/Akt Signaling Pathway Alleviates Oxidative Stress and Neuronal Cell Injury in a Rat Model of Alzheimer’s Disease

Cited by 39 publications

References 38 publications

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats

The Synaptic Vesicle Protein 2A Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment

Memory enhancement effect of saponins from Eleutherococcus senticosus leaves and blood–brain barrier-permeated saponins profiling using a pseudotargeted monitoring strategy

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