Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

Cheng, Xingyi; Song, Chaochun; Du, Yanjiao; Gaur, Uma; Yang, Mingyao

doi:10.3390/ijms21134621

Cited by 17 publications

(11 citation statements)

References 125 publications

(143 reference statements)

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“…Under pathological conditions, APP passes through the neurodegenerative pathway of amyloid. APP can be cut by β-secretase and then cut by γ-secretase to produce Aβ [ 94 ]. The formation of Aβ and its accumulation in the brain can be weakened by stimulating α-secretase.…”

Section: Iron Metabolism and Neurodegenerative Diseasesmentioning

confidence: 99%

Iron Metabolism in Aging and Age-Related Diseases

Tian

Yuan

et al. 2022

IJMS

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Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.

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Section: Iron Metabolism and Neurodegenerative Diseasesmentioning

confidence: 99%

Iron Metabolism in Aging and Age-Related Diseases

Tian

Yuan

et al. 2022

IJMS

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“…This model has the advantage, to some extent, of reducing the use of drugs, which in turn reduces the stress of the experiment and increases the selectivity of ginsenosides, but in this study, the drosophila was modeled as Parkinson's disease [154]. Of course, there have been studies using drosophila models to study pharmacological treatments for AD [228], and there have even been studies on the establishment of a drosophila model for AD [229,230], but there have been few studies on the use of ginsenosides to treat AD using a drosophila model, which is a new and innovative direction.…”

Section: Discussionmentioning

confidence: 99%

American Ginseng for the Treatment of Alzheimer’s Disease: A Review

et al. 2023

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Alzheimer’s disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid β-protein (Aβ) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.

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“…Drosophila do not have an integrated blood-brain barrier, such as that observed in humans, and drugs can easily enter the Drosophila brain, which makes Drosophila an excellent genetic animal model for studying neurodegenerative diseases. In addition, this model has the advantages of low cost, simple feeding methods, short life cycle, strong reproduction ability, large offspring numbers, and ease of phenotype analysis [41,42]. We used the UAS-GAL4 system to hybridize Aβ42-transgenic Drosophila to investigate the effect of aging on Aβ42-transgenic Drosophila as well as the anti-neuroin ammatory and neuroprotective effects of TPPU.…”

Section: Discussionmentioning

confidence: 99%

The soluble epoxide hydrolase inhibitor TPPU alleviates Aβ-mediated neuroinflammatory responses in Drosophila and cellular models of Alzheimer's disease

Sun,

Li,

et al. 2023

Preprint

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Background Alzheimer's disease (AD) is a common neurodegenerative disease, and its pathogenesis is closely associated with neuroinflammation. The control of neuroinflammation in AD is the focus of current research. sEH is increased in the brain tissues of patients with AD, and sEH induces nerve inflammation by degrading epoxyeicosatrienoic acids (EETs). Therefore, sEH inhibitor application and sEH gene knockout are effective ways to improve the bioavailability of EETs and inhibit neuroinflammation in AD. TPPU is a potent sEH inhibitor that has been shown to be effective in preclinical animal models of a variety of chronic inflammatory diseases, we want to further explore whether TPPU can alleviate AD neuroinflammation. Methods In this study, an Aβ42-transgenic Drosophila model was established using the GAL4/UAS system, and the protective and anti-neuroinflammatory effects of TPPU against Aβ toxicity in Drosophila were investigated. Behavioral indexes (survival time, crawling ability, and olfactory memory) and biochemical indexes MDA content and SOD content in brain tissues of Aβ42 transgenic Drosophila were detected. The mRNA expression of the inflammatory cytokines TNF, IL-1 and the gene encoding sEH (EPHX2) in the brain tissue of Aβ42 transgenic drosophila were detected by Real-time PCR. The anti-neuroinflammatory effect of TPPU and its possible mechanism were further explored by stimulating cocultures of SH-SY5Y cells and HMC3 cells with Aβ(25–35) to model neuronal cell inflammation.The cells were detected by fluorescence microscopy, ELISA, Western Blot, and Real-time PCR. Results In vivo drosophila model, we found that TPPU improved the survival time, crawling ability, and olfactory memory of Aβ42-transgenic Drosophila, decreased the MDA content, and increased the SOD content in the brain tissues of Aβ42-transgenic Drosophila. More importantly, TPPU reduced the mRNA expression of the inflammatory cytokines TNF and IL-1 as well as that of the gene encoding sEH (EPHX2) in the brain tissues of Aβ42-transgenic Drosophila. In cell model, we found that TPPU improved cell viability, reduced cell apoptosis, decreased lipid oxidation, inhibited oxidative damage, and enhanced oxygen free radical scavenging, thus playing a neuroprotective role. The mRNA expression of the inflammatory cytokines TNF, IL-1β, IL-6 and IL-18 was downregulated, and the mRNA expression of the M2 microglia markers CD206 and SOCS3 was upregulated by TPPU; thus, TPPU inhibited neuroinflammatory responses. TPPU exerted neuroprotective and anti-inflammatory effects by decreasing the protein expression of the sEH-encoding gene EPHX2 and increasing the levels of 11,12-EET and 14,15-EET. The inhibitory effect of TPPU on Aβ(25–35)-mediated neuroinflammation was associated with inhibition of the TLR4/NF-κB pathway and MAPK/NF-κB pathway. Conclusion We found that the sEH inhibitor TPPU exerts neuroprotective and anti-neuroinflammatory effects in AD models and it is expected that this drug could potentially be used for the prevention and treatment of AD.

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Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

Cited by 17 publications

References 125 publications

Iron Metabolism in Aging and Age-Related Diseases

Iron Metabolism in Aging and Age-Related Diseases

American Ginseng for the Treatment of Alzheimer’s Disease: A Review

The soluble epoxide hydrolase inhibitor TPPU alleviates Aβ-mediated neuroinflammatory responses in Drosophila and cellular models of Alzheimer's disease

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