Studies of neurodegenerative diseases using <i>Drosophila</i> and the development of novel approaches for their analysis

Nitta, Yohei; Sugie, Atsushi

doi:10.1080/19336934.2022.2087484

Cited by 33 publications

(17 citation statements)

References 184 publications

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“…The climbing assay was performed with some modifications, as previously described [ 48 ]. A vertical plastic tube measuring 18 cm in length and 2 cm in diameter was filled with twenty adult flies.…”

Section: Methodsmentioning

confidence: 99%

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

et al. 2022

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Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. This study aimed to compare the ethnopharmacological effects of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) on the amelioration of rotenone-induced toxicity in wild-type Drosophila melanogaster (Oregon R+) at biochemical, cellular, and behavioral levels. Phytoextracts were prepared from all three plants, i.e., UD, MC, and MK (aqueous and ethanolic fractions), and their bioactive compounds were evaluated using in vitro biochemical parameters (DPPH, ABTS, TPC, and TFC), UV-Vis, followed by FT-IR and HPLC. Third instar larvae and freshly eclosed flies were treated with 500 µM rotenone alone or in combination with UD, MC, and MK for 24 to 120 h. Following exposure, cytotoxicity (dye exclusion test), biochemical (protein estimation and acetylcholinesterase inhibition assays), and behavioral assays (climbing and jumping assays) were performed. Among all three plant extracts, MK exhibited the highest antioxidant properties due to the highest TPC, TFC, DPPH, and ABTS, followed by UD, then MC. The overall trend was MK > UD > MC. In this context, ethnopharmacological properties mimic the same effect in Drosophila, exhibiting significantly (p < 0.05) reduced cytotoxicity (trypan blue), improved biochemical parameters (proteotoxicity and AChE activity), and better behavioral parameters in the organisms cotreated with phyto extracts compared with rotenone. Conclusively, UV-Vis, FTIR, and HPLC analyses differentiated the plant extracts. The findings of this research may be beneficial in the use of select herbs as viable sources of phyto-ingredients that could be of interest in nutraceutical development and various clinical applications.

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Section: Methodsmentioning

confidence: 99%

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

et al. 2022

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“…The Drosophila eye consists of 700–800 basic units called ommatidia. They are aligned in an orderly manner but become disordered with the infusion of ectopic genes that function within them 19 . Rough-eye phenotype can be performed without special equipment other than an epimicroscope.…”

Section: Discussionmentioning

confidence: 99%

A novel NONO variant that causes developmental delay and cardiac phenotypes

Itai

Sugie

Nitta

et al. 2023

Sci Rep

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The Drosophila behavior/human splicing protein family is involved in numerous steps of gene regulation. In humans, this family consists of three proteins: SFPQ, PSPC1, and NONO. Hemizygous loss-of-function (LoF) variants in NONO cause a developmental delay with several complications (e.g., distinctive facial features, cardiac symptoms, and skeletal symptoms) in an X-linked recessive manner. Most of the reported variants have been LoF variants, and two missense variants have been reported as likely deleterious but with no functional validation. We report three individuals from two families harboring an identical missense variant that is located in the nuclear localization signal, NONO: NM_001145408.2:c.1375C > G p.(Pro459Ala). All of them were male and the variant was inherited from their asymptomatic mothers. Individual 1 was diagnosed with developmental delay and cardiac phenotypes (ventricular tachycardia and dilated cardiomyopathy), which overlapped with the features of reported individuals having NONO LoF variants. Individuals 2 and 3 were monozygotic twins. Unlike in Individual 1, developmental delay with autistic features was the only symptom found in them. A fly experiment and cell localization experiment showed that the NONO variant impaired its proper intranuclear localization, leading to mild LoF. Our findings suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.

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“…Strikingly, beside their role in ommochrome biosynthesis, Drosophila cn /KMO and st can modulate degeneration in neurons in disease models such as Huntington’s (Campesan, Green et al, 2011, Green, Campesan et al, 2012) and Parkinson’s Disease (Cunningham, Waldeck et al, 2018). These data together with the high degree of genetic conservation of disease genes in Drosophila support the fly model as a valuable system to unravel the underlying genetic and molecular basis of neurodegenerative diseases (Nitta & Sugie, 2022, Ugur, Chen et al, 2016), including retinal degeneration (Lehmann, Knust et al, 2019).…”

Section: Introductionmentioning

confidence: 83%

Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light induced damage in Drosophila

Hebbar

Traikov

Hälsig

et al. 2022

Preprint

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Tissue health is regulated by a myriad of exogenous or endogenous factors. Here we investigated the role of the conserved Kynurenine pathway (KP) in maintaining retinal homeostasis in the context of light stress in Drosophila melanogaster. cinnabar, cardinal and, scarlet, are fly genes that encode different steps in the KP. Along with white, these genes are known regulators of brown pigment (ommochrome) biosynthesis. Using white as a sensitized genetic background, we showed that mutations in cinnabar, cardinal, and scarlet differentially modulate light-induced retinal damage. Mass Spectrometric measurements of KP metabolites in flies with different genetic combinations support the notion that increased levels of 3-hydroxykynurenine (3OH-K) and Xanthurenic acid (XA) enhance retinal damage, whereas Kynurenic Acid (KYNA) and Kynurenine (K) are neuro-protective. This conclusion was corroborated by showing that feeding 3OH-K results in enhanced retinal damage, whereas feeding KYNA protects the retina in sensitized genetic backgrounds. Interestingly, the harmful effects of free 3OH-K are diminished by its sub-cellular compartmentalization within the cell. Sequestering of 3OH-K enables the quenching of its toxicity through conversion to brown pigment or conjugation to proteins. This work enabled us to decouple the role of these KP genes in ommochrome formation from their role in retinal homeostasis. Additionally, it puts forward new hypotheses on the importance of the balance of KP metabolites and their compartmentalization in disease alleviation.

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Studies of neurodegenerative diseases using Drosophila and the development of novel approaches for their analysis

Cited by 33 publications

References 184 publications

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers

A novel NONO variant that causes developmental delay and cardiac phenotypes

Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light induced damage in Drosophila

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