Genistein attenuates memory impairment in Alzheimer's disease via ERS-mediated apoptotic pathway in vivo and in vitro

Gao, Hua-Wu; Lei, Xin Gen; Ye, Shu; Ye, Ting; Hua, Rupeng; Wang, Guoquan; Song, Hang; Zhou, Peng; Wang, Yan; Cai, Biao

doi:10.1016/j.jnutbio.2022.109118

Cited by 13 publications

(8 citation statements)

References 35 publications

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“…The Bcl-2 family has both anti-apoptotic and pro-apoptotic effects. Genistein (GS) plays a neuroprotective role in Alzheimer’s disease (AD) by inhibiting the ER-mediated apoptotic pathway ( 18 ), and the anti-apoptotic gene survivin is a therapeutic target in malignant rhabdoid tumor (MRT) and other SMARCB1/INI1-deficient tumors ( 19 - 21 ). Table 4 illustrates the various potential apoptotic genes of the hERG/G572R channel, which may be a new way to find the treatment of inherited gene mutation diseases.…”

Section: Discussionmentioning

confidence: 99%

4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene

Tang,

Cai,

et al. 2023

J Thorac Dis

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Background Long QT syndrome type 2 (LQT2) is caused by mutations in the KCNH2 /human ether-à-go-go-related gene (hERG). Some hERG genetic mutation-associated diseases are alleviated by hERG-specific drug chaperones (glycerol, dimethyl sulfoxide, trimethylamine N-oxide, thapsigargin), delayed rectifier K + current (IKr) blockers methanesulfonanilide E4031, the antihistamine astemizole, or the prokinetic drug cisapride, and the anti-arrhythmic drug quinidine. Meanwhile, many in vivo and in vitro studies have reported the efficacy of 4-phenylbutyric acid (4-PBA) in diseases with inherited genetic mutations. This study aims to explore potential therapeutic agents for hERG/G572R mutated ion channel. Methods pcDNA3/hERG [wild type (WT)]-FLAG and pcDNA3/hERG (G572R)-FLAG plasmids were transfected into HEK293 cells. A western blot (WB) experiment was conducted to analyze protein expression. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the messenger RNA (mRNA) expression levels in the WT/G572R heterozygous HEK293 cell model treated with or without 4-PBA. The interaction between WT/G572R and BIP (GRP78), GRP94, and 3-hydroxy-3-methylglutaryl coenzyme A reductase degradation protein 1 (HRD1) was tested by co-immunoprecipitation (co-IP). To investigate the effect of 4-PBA on the WT/G572R channel current, we used electrophysiological assays (patch-clamp electrophysiological recordings). Results The results showed that WT/G572R activated the ATF6 pathway in the endoplasmic reticulum stress (ERS), the ERS response markers GRP78, GRP94, and calreticulin (CRT)/calnexin (CNX), and HRD1, which decreased after application of the ERS inhibitor 4-PBA. The results of co-IP confirmed that the ability of hERG interacted with GRP78, GRP94, and HRD1. Moreover, 4-PBA increased the current of WT/G572R and reversed the gating kinetics of the WT/G572R channel. Conclusions 4-PBA corrects hERG channel transport defects by inhibiting excessive ERS and the endoplasmic reticulum-associated degradation (ERAD)-related gene E3 ubiquitin ligase HRD1. Additionally, 4-PBA improved WT/G572R channel current. 4-PBA is expected to be developed as a new treatment method for LQT2.

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Section: Discussionmentioning

confidence: 99%

4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene

Tang,

Cai,

et al. 2023

J Thorac Dis

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“…Additionally, to enhance the understanding of the potential mechanism and therapeutic role of Scutellaria baicalensis in Alzheimer’s Disease, we recommend conducting future in vivo studies using a rat model to measure learning and memory abilities using Radial Arm Maze (RAM) tools and observe the morphological changes of the rat hippocampus using immunohistochemistry. 4 , 5 These in vivo tests can provide insights into how the bioactive compounds of Scutellaria baicalensis may improve learning and memory abilities and reduce damage to hippocampal neurons to prevent Alzheimer’s disease. 5 Overall, we congratulate all authors who have provided important information regarding offering bioactive compounds for Scutellaria baicalensis prospective therapeutic efficacy against Alzheimer’s disease, presenting valuable insights for subsequent clinical drug advancement.…”

Section: Dear Editormentioning

confidence: 99%

“… 4 , 5 These in vivo tests can provide insights into how the bioactive compounds of Scutellaria baicalensis may improve learning and memory abilities and reduce damage to hippocampal neurons to prevent Alzheimer’s disease. 5 Overall, we congratulate all authors who have provided important information regarding offering bioactive compounds for Scutellaria baicalensis prospective therapeutic efficacy against Alzheimer’s disease, presenting valuable insights for subsequent clinical drug advancement.…”

Section: Dear Editormentioning

confidence: 99%

Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role of Scutellaria baicalensis in Alzheimer’s Disease [Letter]

Yulion,

Andriani,

Aliyah

2024

DDDT

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“…These results suggest that genistein exerts a neuroprotective effect by inhibiting the ERS-mediated apoptotic pathway and may be a new target for the treatment of AD. 62 7.2.4. Anti-Inflammatory.…”

Section: Anti-aβ Depositionmentioning

confidence: 99%

Genistein in the Treatment of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Lei,

Dong,

Gao

2024

J. Agric. Food Chem.

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Genistein is a phytoestrogen distributed in fruits, seeds, and vegetables that holds great promise against a variety of Aβ-induced damage. However, the exact molecular mechanisms underlying the neuroprotective effects of genistein on Alzheimer's disease (AD) remain unknown. Here, we assessed the potential mechanisms and effectiveness of genistein for AD treatment using a systematic review and meta-analysis of preclinical trials. Preclinical studies published prior to September 21, 2022 were retrieved from Web of Science, PubMed, CNKI, and CBM. The CAMARADES list was used to evaluate the quality of included studies. Metaanalyses of AD pathology and animal model studies evaluating parameters and other indicators were performed. Overall, 14 articles involving more than 800 animals were included. We analyzed in vivo and in vitro studies about genistein's effects, including antiamyloidogenesis, antioxidation, antiapoptosis, inhibition of inflammation, and improvement of the lipid composition of neurons. In behavioral assessment, genistein significantly improved the time in the platform quadrant (I 2 = 76%, p < 0.00001) in the Morris water maze test, spontaneous alternation behavior (I 2 = 94%, p < 0.00001) in Y-maze tests, and the time entering the dark compartment (I 2 = 81%, p = 0.02) in a single-trial passive avoidance test. Genistein therapy in rodent models of AD indicates it reduces Aβ deposition and improves memory in preclinical trials.

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Genistein attenuates memory impairment in Alzheimer's disease via ERS-mediated apoptotic pathway in vivo and in vitro

Cited by 13 publications

References 35 publications

4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene

4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene

Network Pharmacology and Molecular Docking Identify the Potential Mechanism and Therapeutic Role of Scutellaria baicalensis in Alzheimer’s Disease [Letter]

Genistein in the Treatment of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

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