Effects of sarah/nebula knockdown on Aβ42-induced phenotypes during Drosophila development

Bang, Se Min; Lee, Soojin; Jeong, Haemin; Hong, Yong Deog; Lee, Jang Ho; Hwang, Soon Jae; Suh, Yoon Seok; Lee, Kyung-Ho; Cho, Kyoung Sang

doi:10.1007/s13258-016-0407-5

Cited by 2 publications

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References 48 publications

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“…Based on well-developed genetic tools, such as the upstream activation sequence ( UAS ) -GAL4 system, by which the expression of desired genes can be regulated, Drosophila has been used as an animal model to study AD (Lee et al 2014 , 2016 ; Bang et al 2016 ). To date, different groups have generated several different transgenic lines that can be used for the ectopic expression of human Aβ42 .…”

Section: Introductionmentioning

confidence: 99%

Phenotypic differences between Drosophila Alzheimer’s disease models expressing human Aβ42 in the developing eye and brain

Jeon

Lee

Shin

et al. 2017

Animal Cells and Systems

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Drosophila melanogaster expressing amyloid-β42 (Aβ42) transgenes have been used as models to study Alzheimer’s disease. Various Aβ42 transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently used Aβ42 transgenic lines, UAS-Aβ422X, UAS-Aβ42BL33770, UAS-Aβ4211C39, and UAS-Aβ42H29.3. Among the four transgenic lines, only UAS-Aβ422X has two copies of the upstream activation sequence-amyloid-β42 (UAS-Aβ42) transgene, while remaining three have one copy. UAS-Aβ42BL33770 has the 3′ untranslated region of Drosophila α-tubulin, while the others have that of SV40. UAS-Aβ4211C39 and UAS-Aβ42H29.3 have the rat pre-proenkephalin signal peptide, while UAS-Aβ422X and UAS-Aβ42BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-Aβ422X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-Aβ42BL33770 only showed a strong rough eye phenotype; UAS-Aβ42H29.3 and UAS-Aβ4211C39 had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in UAS-Aβ422X, followed by UAS-Aβ42BL33770, UAS-Aβ4211C39, and UAS-Aβ42H29.3. Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed UAS-Aβ4211C39 or UAS-Aβ42H29.3 experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different Drosophila AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity.Abbreviations: Aβ42: amyloid-β42; AD: Alzheimer’s disease; UAS: upstream activation sequence

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Section: Introductionmentioning

confidence: 99%

Phenotypic differences between Drosophila Alzheimer’s disease models expressing human Aβ42 in the developing eye and brain

Jeon

Lee

Shin

et al. 2017

Animal Cells and Systems

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<i>Nardostachys jatamansi</i> Ethanol Extract Ameliorates Aβ42 Cytotoxicity

Liu

Jeon

Sung

et al. 2018

Biological & Pharmaceutical Bulletin

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SummaryThe Nardostachys jatamansi DC (NJ) root has been used as a sedative or analgesic to treat neurological symptoms and pain in traditional Korean medicine. Here, we investigate the potential effects of NJ on Alzheimer's disease (AD) and reveal the molecular mechanism through which NJ exerts its effects. The neuroprotective effect of the NJ root ethanol extract against β amyloid (Aβ) toxicity was examined in vitro using a cell culture system and in vivo using a Drosophila AD model. The NJ extract and chlorogenic acid, a major component of NJ, inhibited Aβ-induced cell death in SH-SY5Y cells. Moreover, the NJ extract rescued the neurological phenotypes of the Aβ42-expressing flies (decreased survival and pupariation rate and a locomotor defect) and suppressed Aβ42-induced cell death in the brain. We also found that NJ extract intake reduced glial cell number, reactive oxygen species level, extracellularsignal-regulated kinase (ERK) phosphorylation, and nitric oxide level in Aβ42-expressing flies, without affecting Aβ accumulation. These data suggest that the neuroprotective activity of NJ might be associated with its antioxidant and anti-inflammatory properties, as well as its inhibitory action against ERK signaling; thus, NJ is a promising medicinal plant for the development of AD treatment.

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Effects of sarah/nebula knockdown on Aβ42-induced phenotypes during Drosophila development

Cited by 2 publications

References 48 publications

Phenotypic differences between Drosophila Alzheimer’s disease models expressing human Aβ42 in the developing eye and brain

Phenotypic differences between Drosophila Alzheimer’s disease models expressing human Aβ42 in the developing eye and brain

<i>Nardostachys jatamansi</i> Ethanol Extract Ameliorates Aβ42 Cytotoxicity

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