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Effect of kaempferol on the transgenic Drosophila model of Parkinson's disease.

ABSTRACT: The present study was aimed to study the effect of kaempferol, on the transgenic Drosophila model of Parkinson's disease. Kaempferol was added in the diet at final concentration of 10, 20, 30 and 40 µM and the effect was studied on various cognitive and oxidative stress markers. The results of the study showed that kaempferol, delayed the loss of climbing ability as well as the activity of PD flies in a dose dependent manner compared to unexposed PD flies. A dose-dependent reduction in oxidative stress markers was also observed. Histopathological examination of fly brains using anti-tyrosine hydroxylase immunostaining has revealed a significant dose-dependent increase in the expression of tyrosine hydroxylase in PD flies exposed to kaempferol. Molecular docking results revealed that kaempferol binds to human alpha synuclein at specific sites that might results in the inhibition of alpha synuclein aggregation and prevents the formation of Lewy bodies.

SUBMITTER: Rahul

PROVIDER: S-EPMC7429503 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Effect of kaempferol on the transgenic Drosophila model of Parkinson's disease.

Rahul Naz Falaq F Jyoti Smita S Siddique Yasir Hasan YH

Scientific reports 20200814 1

The present study was aimed to study the effect of kaempferol, on the transgenic Drosophila model of Parkinson's disease. Kaempferol was added in the diet at final concentration of 10, 20, 30 and 40 µM and the effect was studied on various cognitive and oxidative stress markers. The results of the study showed that kaempferol, delayed the loss of climbing ability as well as the activity of PD flies in a dose dependent manner compared to unexposed PD flies. A dose-dependent reduction in oxidative ...[more]

PMID: 32796885

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Effect of curcumin on lifespan, activity pattern, oxidative stress, and apoptosis in the brains of transgenic Drosophila model of Parkinson's disease.

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Effect of Majun Baladur on life span, climbing ability, oxidative stress and dopaminergic neurons in the transgenic <i>Drosophila</i> model of Parkinson's disease.

Project description:The effect of a poly herbal drug Majun Baladur (MB) was studied on the transgenic Drosophila melanogaster expressing human alpha synuclein in the neurons (PD flies). The equivalents of recommended dose for human were established for 20 g of fly food i.e. 0.0014, 0.0028, 0.0042 and 0.0056 g per 20 g of diet. The PD flies were allowed to feed on it for 24 days before performing the assays. The exposure to MB increased the life span and improves the activity of PD flies. The PD flies exposed to 0.0014, 0.0028, 0.042 and 0.0056 g of MB showed a dose dependent significant delay of 1.47, 1.88, 2.52 and 3.05 folds in the climbing ability compared to unexposed PD flies. A dose dependent significant decrease of 1.38, 1.45, 1.48 and 1.65 folds in TBARS; 1.08, 1.11, 1.17 and 1.20 folds in the GST activity; 1.20, 1.28, 1.39 and 1.52 folds in the PC content; 1.43, 1.53, 1.65 and 1.79 folds in the Caspase-9 activity; 1.21, 1.31, 1.53 and 1.64 folds in the activity of Caspase-3 and 1.24, 1.42, 1.50 and 1.79 folds in the activity of catalase; 1.50, 1.63, 1.88 and 2.06 folds in the activity of SOD in PD flies exposed to 0.0014, 0.0028, 0.042 and 0.0056 g of MB, respectively. A significant dose dependent increase of 1.20, 1.29, 1.33 and 1.44 folds in as NPSH content was observed in PD flies exposed to 0.0014, 0.0028, 0.042 and 0.0056 g of MB, respectively. The exposure to MB protects the loss of dopaminergic neurons as is evident by immunohistochemistry. It is concluded that MB is potent in reducing the PD symptoms being mimicked in the transgenic flies.

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2012-09-05 | E-GEOD-35930 | biostudies-arrayexpress

Effect of paraquat and nicotine on gene expression in a Drosophila melanogaster Parkinson's disease model

2012-09-05 | GSE35930 | GEO

An altered microbiome in a Parkinson's disease model Drosophila melanogaster has a negative effect on development.

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Project description:Disease phenotypes can be highly variable among individuals with the same pathogenic mutation. There is increasing evidence that background genetic variation is a strong driver of disease variability in addition to the influence of environment. To understand the genotype-phenotype relationship that determines the expressivity of a pathogenic mutation, a large number of backgrounds must be studied. This can be efficiently achieved using model organism collections such as the Drosophila Genetic Reference Panel (DGRP). Here, we used the DGRP to assess the variability of locomotor dysfunction in a LRRK2 G2019S Drosophila melanogaster model of Parkinson's disease (PD). We find substantial variability in the LRRK2 G2019S locomotor phenotype in different DGRP backgrounds. A genome-wide association study for candidate genetic modifiers reveals 177 genes that drive wide phenotypic variation, including 19 top association genes. Genes involved in the outgrowth and regulation of neuronal projections are enriched in these candidate modifiers. RNAi functional testing of the top association and neuronal projection-related genes reveals that pros, pbl, ct, and CG33506 significantly modify age-related dopamine neuron loss and associated locomotor dysfunction in the Drosophila LRRK2 G2019S model. These results demonstrate how natural genetic variation can be used as a powerful tool to identify genes that modify disease-related phenotypes. We report novel candidate modifier genes for LRRK2 G2019S that may be used to interrogate the link between LRRK2, neurite regulation and neuronal degeneration in PD.

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Transgenic rodent models of Parkinson's disease.

Project description:In the case of Parkinson's disease (PD), classical animal models have utilized dopaminergic neurotoxins such as 6-hydroxydopamine (6OHDA) and 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). More recently, human genetic linkage studies have identified several genes in familial forms of PD. Transgenic models have been made that explore the function of PD-linked genes (e.g. alpha-synuclein, DJ-1, LRRK2, Parkin, UCH-L1, PINK1). Recent evidence suggests mitochondrial dysfunction may play a major role in PD. Manipulation of mitochondrial respiratory genes (e.g. mitochondrial transcription factor A or TFAM) also elicits a PD phenotype in mice. Transgenic mice (MitoPark) were developed that have TFAM selectively knocked out in dopaminergic neurons. The nigral dopamine neurons of MitoPark mice show respiratory chain dysfunction, accompanied by the development of intraneuronal inclusions and eventual cell death. In early adulthood, the MitoPark mice show a slowly progressing loss of motor function that accompanies these cellular changes. The MitoPark mouse enables further study of the role of mitochondrial dysfunction in DA neurons as an important mechanism in the development of PD. Transgenic technology has allowed new insights into mechanisms of neurodegeneration for a number of neurological disorders. This paper will summarize recent studies on several transgenic models of PD.

| S-EPMC2613245 | biostudies-literature

SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.

Project description:The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. Mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dementia with Lewy bodies. We previously described a transgenic mouse line expressing truncated human alpha-synuclein(1-120) that develops alpha-synuclein aggregates, striatal dopamine deficiency and reduced locomotion, similar to Parkinson's disease. We now show that in the striatum of these mice, as in Parkinson's disease, synaptic accumulation of alpha-synuclein is accompanied by an age-dependent redistribution of the synaptic SNARE proteins SNAP-25, syntaxin-1 and synaptobrevin-2, as well as by an age-dependent reduction in dopamine release. Furthermore, the release of FM1-43 dye from PC12 cells expressing either human full-length alpha-synuclein(1-140) or truncated alpha-synuclein(1-120) was reduced. These findings reveal a novel gain of toxic function of alpha-synuclein at the synapse, which may be an early event in the pathogenesis of Parkinson's disease.

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