Insulin signaling in Drosophila melanogaster mediates Aβ toxicity

Huang, Yunpeng; Wan, Zhaohui; Wang, Zhiqing; Zhou, Bing

doi:10.1038/s42003-018-0253-x

Cited by 18 publications

(13 citation statements)

References 63 publications

(70 reference statements)

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“…Neuropeptides and insulin signaling have been implicated in multiple aspects of sex-specific behavior and physiology including mating and reproduction 23,24 , and, as our data indicate, brain-expressed Tud may partially contribute to these processes in Drosophila. Interestingly, a recent study also showed the upregulation of tobi in the fly heads in response to the accumulation of β-amyloid peptide (Aβ) in the Alzheimer's disease Drosophila model 25 .…”

Section: Resultsmentioning

confidence: 99%

Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome

2020

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Membraneless RNA-protein granules play important roles in many different cell types and organisms. In particular, granules found in germ cells have been used as a paradigm to study large and dynamic granules. These germ granules contain RNA and proteins required for germline development. Here, we unexpectedly identify large granules in specific subtypes of glial cells (“glial granules”) of the adult Drosophila brain which contain polypeptides with previously characterized roles in germ cells including scaffold Tudor, Vasa, Polar granule component and Piwi family proteins. Interestingly, our super-resolution microscopy analysis shows that in the glial granules, these proteins form distinct partially overlapping clusters. Furthermore, we show that glial granule scaffold protein Tudor functions in silencing of transposable elements and in small regulatory piRNA biogenesis. Remarkably, our data indicate that the adult brain contains a small population of cells, which express both neuroblast and germ cell proteins. These distinct cells are evolutionarily conserved and expand during aging suggesting the existence of age-dependent signaling. Our work uncovers previously unknown glial granules and indicates the involvement of their components in the regulation of brain transcriptome.

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Section: Resultsmentioning

confidence: 99%

Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome

2020

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“…PPARγ is a transcription factor that is present in the BACE1 promoter and reduces BACE1 activity (Chen et al, 2012) and transcriptionally regulates the expression of IDE in primary neurons (Du et al, 2009). Some studies have also demonstrated that IDE could reduce Aβ toxicity and promote Aβ clearance (Huang et al, 2019) as well as reduce the level of IDE or genetic mutation of IDE-altered AD pathology (Cook et al, 2003;Prince et al, 2003). To elucidate the mechanism of BEOV in inhibiting Aβ production and promoting Aβ clearance in the brain of APPSwe/PS1dE9 mice, the expression levels of PPARγ and IDE were assessed by Western blot analyses.…”

Section: Beov Up-regulated the Expression Of Pparγ And Ide In The Ad mentioning

confidence: 99%

The Protective Effect of Vanadium on Cognitive Impairment and the Neuropathology of Alzheimer’s Disease in APPSwe/PS1dE9 Mice

Han

Zhu

et al. 2020

Front. Mol. Neurosci.

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Alzheimer's disease (AD) is a widely distributed neurodegenerative disease characterized clinically by cognitive deficits and pathologically by formation of amyloid-β (Aβ) plaque and neurofibrillary tangles (NFTs) in the brain. Vanadium is a biological trace element that has a function to mimic insulin for diabetes. Bis(ethylmaltolato) oxidovanadium (IV) (BEOV) has been reported to have a hypoglycemic property, but its effect on AD remains unclear. In this study, BEOV was supplemented at doses of 0.2 and 1.0 mmol/L to the AD model mice APPSwe/PS1dE9 for 3 months. The results showed that BEOV substantially ameliorated glucose metabolic disorder as well as synaptic and behavioral deficits of the AD mice. Further investigation revealed that BEOV significantly reduced Aβ generation by increasing the expression of peroxisome proliferator-activated receptor gamma and insulin-degrading enzyme and by decreasing β-secretase 1 in the hippocampus and cortex of AD mice. BEOV also reduced tau hyperphosphorylation by inhibiting protein tyrosine phosphatase-1B and regulating the pathway of insulin receptor/insulin receptor substrate-1/protein kinase B/glycogen synthase kinase 3 beta. Furthermore, BEOV could enhance autophagolysosomal fusion and restore autophagic flux to increase the clearance of Aβ deposits and phosphorylated tau in the brains of AD mice. Collectively, the present study provides solid data for revealing the function and mechanism of BEOV on AD pathology.

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“…1 f). In addition, FOXO is a downstream component of insulin/IGF signaling pathway, which modulation may be associated with Aβ toxicity [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Amyloid-β peptides slightly affect lifespan or antimicrobial peptide gene expression in Drosophila melanogaster

et al. 2020

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Background Beta-amyloid peptide (Aβ) is the key protein in the pathogenesis of Alzheimer’s disease, the most common age-related neurodegenerative disorder in humans. Aβ peptide induced pathological phenotypes in different model organisms include neurodegeneration and lifespan decrease. However, recent experimental evidence suggests that Aβ may utilize oligomerization and fibrillization to function as an antimicrobial peptide (AMP), and protect the host from infections. We used the power of Drosophila model to study mechanisms underlying a dual role for Aβ peptides. Results We investigated the effects of Drosophila treatment with three Aβ42 peptide isoforms, which differ in their ability to form oligomers and aggregates on the lifespan, locomotor activity and AMP genes expression. Aβ42 slightly decreased female’s median lifespan (by 4.5%), but the effect was not related to the toxicity of peptide isoform. The lifespan and relative levels of AMP gene expression in male flies as well as locomotor activity in both sexes were largely unaffected by Aβ42 peptide treatment. Regardless of the effects on lifespan, Aβ42 peptide treatment induced decrease in AMP genes expression in females, but the effects were not robust. Conclusions The results demonstrate that chronic treatment with Aβ42 peptides does not drastically affect fly aging or immunity.

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Insulin signaling in Drosophila melanogaster mediates Aβ toxicity

Cited by 18 publications

References 63 publications

Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome

Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome

The Protective Effect of Vanadium on Cognitive Impairment and the Neuropathology of Alzheimer’s Disease in APPSwe/PS1dE9 Mice

Amyloid-β peptides slightly affect lifespan or antimicrobial peptide gene expression in Drosophila melanogaster

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