Exendin-4 alleviates β-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis elegans model of Alzheimer's disease

Song, Xiangwei; Sun, Yangying; Wang, Zhun; Su, Yingying; Wang, Yangkun; Wang, Xueli

doi:10.3389/fnagi.2022.955113

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…C. elegans skn-1, which plays an important role in regulatory pathways and treatments to increase life span, is significantly homologous to Nrf2, a regulatory protein for antioxidant and xeno defense [ 33 ]. Daf-16 and skn-1 play necessary roles in lowering Aβ aggregation, and daf-16 regulates the insulin/insulin-like growth factor receptor signaling system (IIS), which has been linked to transcriptional alterations in genes related to aging, development, stress, metabolism, and immunity [ 25 ]. Hsf-1 reduces Aβ proteotoxicity in the AD model of C. elegans [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

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Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

Yan,

Deng,

et al. 2024

Metabolites

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Smilax china L. (Chinaroot) is a natural herb that has multiple uses, such as being used to make tea and food. Both its roots and leaves have different uses due to their unique components. In this study, we analyzed the extract of S. china. roots using LC-HRMS and evaluated the neuroprotective effects and metabolic regulation of S. china on Caenorhabditis elegans. Chinaroot extract prolonged the life span of healthy nematodes, delayed the paralysis time of transgenic CL4176, and reduced the level of β-amyloid deposition in transgenic CL2006. The comprehensive analysis of metabolomics and qRT-PCR revealed that Chinaroot extract exerted neuroprotective effects through the valine, leucine and isoleucine degradation and fatty acid degradation pathways. Moreover, we first discovered that the expressions of T09B4.8, ech-7, and agxt-1 were linked to the neuroprotective effects of Chinaroot. The material exerted neuroprotective effects by modulating metabolic abnormalities in AD model C. elegans. Our study provides a new foundation for the development of functional food properties and functions.

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Section: Resultsmentioning

confidence: 99%

“…Wild-type N2 C. elegans was used for reproductive capacity and body length assay [ 25 ]. N2 hermaphrodite C. elegans specimens synchronized to L4 were randomly assigned to NGM plates coated with control (0.1% DMSO) or ScE (1, 10, 50 and 100 μg/mL) groups.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

Yan,

Deng,

et al. 2024

Metabolites

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“…With reference to Song et al (6), CL4176 nematodes were synchronized at 16˚C for 48 h, cultured at 25˚C for 40 h then rinsed twice with M9 buffer to remove E. coli. The nematodes were then homogenized and protein abundance was measured by the bicinchoninic acid assay (Beyotime Institute of Biotechnology).…”

Section: Measurement Of Ros Malondialdehyde (Mda) Superoxide Dismutas...mentioning

confidence: 99%

“…Aβ aggregation can have a direct toxic effect on nerve cells, and oligomers formed by Aβ aggregation can stimulate the graded activation of inflammation and oxidative stress, which in turn promote further Aβ aggregation in a positive feedback loop (3,4). Therefore, the mechanism of Aβ deposition in AD has been increasingly investigated in recent years (5)(6)(7)(8). The drugs currently used to treat AD are symptomatic and have very limited effects on improving the course of the disease (9).…”

Section: Introductionmentioning

confidence: 99%

Ethyl acetate extract of Gastrodia elata protects Caenorhabditis elegans from oxidative stress and amyloid β peptide toxicity

Shi

Yang

et al. 2023

Exp Ther Med

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Gastrodia elata Blume is a traditional Chinese medicine with a long history, which has numerous pharmacological activities, such as anti-inflammation, anti-oxidation and protection of nerves. The present study investigated the regulatory effect of ethyl acetate extract of Gastrodia elata (EEGE) on the β-amyloid (Aβ) toxicity of Caenorhabditis elegans (C. elegans). First, the main components of EEGE were analyzed using high-performance liquid chromatography, and the total phenols, total flavonoids and total antioxidant capacity of EEGE were determined. Next, the regulation effect of EEGE on Aβ-induced toxicity of C. elegans was evaluated through experiments on nematode paralysis, lifespan, oxidative and heat stress, locomotor ability, reproductive ability, reactive oxygen species (ROS) level, Aβ aggregation test, malondialdehyde (MDA) level, catalase (CAT) activity and superoxide dismutase (SOD) activity. Finally, the mechanism of EEGE was elucidated using RNA sequencing (RNA-Seq) and the expression levels of related genes were verified using quantitative PCR. The present study revealed that the main components of EEGE included phosphorylated (p)-hydroxybenzyl alcohol, p-hydroxybenzaldehyde and 4,4'-dihydroxydiphenylmethane, possessing strong in vitro free radical scavenging and reducing abilities. In addition, after the intervention of EEGE, the paralysis of nematodes could be delayed, the survival time of the nematodes was prolonged, the survival rate of the nematodes under stress (high temperature and oxidation) conditions was improved, the activity capacity and reproductive capacity of the nematodes were improved, the activities of SOD and CAT were improved and the levels of ROS and MDA were reduced. Notably, EEGE directly inhibited Aβ plaque aggregation in nematodes. RNA-Seq analysis showed that EEGE regulated metabolism and longevity-related genes, and these genes were regulated by the insulin/IGF-1 signaling (IIS) pathway. Therefore, the present study hypothesized that the regulatory mechanism of EEGE was significantly related to the IIS pathway. The present research results demonstrated that the protective effect of EEGE on transgenic C. elegans was to reduce Aβ protein aggregation, improve the in vivo antioxidant level, effectively remove free radicals and to regulate the expression of genes related to IIS pathway, thereby reducing Aβ-induced toxicity and delaying nematode paralysis.

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“…A recent study examined the neuroprotective potential of exendin‐4 in transgenic Caenorhabditis elegans, marking the first instance of such an investigation. The outcomes of the study showed that exendin‐4 effectively reduced the harmful effects of Aβ 1‐42 in the C. elegans AD model by lowering both the expression and buildup of Aβ 1‐42 (Song et al., 2022).…”

Section: Exendin‐4 In Preclinical Models Of Alzheimer's Diseasementioning

confidence: 99%

Exendin‐4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease

Verma,

Chaudhary,

Solanki

et al. 2023

Chem Biol Drug Des

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Neurodegenerative disorders, which affect millions worldwide, are marked by a steady decline of neurons that are selectively susceptible. Due to the complex pathological processes underlying neurodegeneration, at present, there is no viable therapy available for neurodegenerative disorders. Consequently, the establishment of a novel therapeutic approach for such conditions is a clinical void that remains. The potential significance of various peptides as neuroprotective interventions for neurodegenerative disorders is gaining increasing attention. In the past few years, there has been growing scientific interest in glucagon‐like peptide‐1 receptor agonists due to their claimed neuroprotective effects. Exendin‐4 is a glucagon‐like peptide‐1 receptor agonist that is known to possess anti‐diabetic effects and does not degrade for hours, making it a superior candidate for such disorders. Moreover, exendin‐4's neuroprotective effects have been reported in several preclinical studies. Exendin‐4's diverse therapeutic targets suggest its potential therapeutic uses in neurodegenerative ailments like Alzheimer's disease and Parkinson's disease and have garnered an increasing amount of attention. Given the substantial body of evidence supporting the neuroprotective potential of exendin‐4 in various research models, this article is dedicated to exploring the promising role of exendin‐4 as a therapeutic agent for the treatment and management of Alzheimer's disease and Parkinson's disease. This review draws insights from the findings of numerous preclinical and clinical studies to highlight the collective neuroprotective advantages of exendin‐4 and the potential mechanisms that underlie its neuroprotective effects.

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Exendin-4 alleviates β-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis elegans model of Alzheimer's disease

Cited by 17 publications

References 37 publications

Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

Ethyl acetate extract of Gastrodia elata protects Caenorhabditis elegans from oxidative stress and amyloid β peptide toxicity

Exendin‐4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease

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