Mutant α-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson's disease

Genome ◽  
2006 ◽  
Vol 49 (5) ◽  
pp. 505-510 ◽  
Author(s):  
Annika F.M Haywood ◽  
Brian E Staveley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Retinal Degeneration ◽  
Ubiquitin Ligase ◽  
Dopaminergic Neurons ◽  
Genetic Model ◽  
Protein Functions ◽  
Climbing Ability ◽  
Mutant Forms

Parkinson's disease (PD) patients show a characteristic loss of motor control caused by the degeneration of dopaminergic neurons. Mutations in the genes that encode α-synuclein and parkin have been linked to inherited forms of this disease. The parkin protein functions as a ubiquitin ligase that targets proteins for degradation. Expression of isoforms of human α-synuclein in the Drosophila melanogaster nervous system forms the basis of an excellent genetic model that recapitulates phenotypic and behavioural features of PD. Using this model, we analysed the effect of parkin co-expression on the climbing ability of aging flies, their life span, and their retinal degeneration. We have determined that co-expression of parkin can suppress phenotypes caused by expression of mutant α-synuclein. In the developing eye, parkin reduces retinal degeneration. When co-expressed in the dopaminergic neurons, the ability to climb is extended over time. If conserved in humans, we suggest that upregulation of parkin may prove a method of suppression for PD induced by mutant forms of α-synuclein.Key words: parkin, α-synuclein, Drosophila melanogaster, model of Parkinson's disease.

The HtrA2 Drosophila model of Parkinson’s disease is suppressed by the pro-survival Bcl-2 Buffy

Genome ◽  
2017 ◽  
Vol 60 (1) ◽  
pp. 1-7 ◽  
Author(s):  
P. Githure M’Angale ◽  
Brian E. Staveley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
High Temperature ◽  
Dopaminergic Neurons ◽  
Inhibitors Of Apoptosis ◽  
Drosophila Model ◽  
Age Dependent ◽  
Climbing Ability ◽  
Locomotor Ability

Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson’s disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy.

The FBXO7 homologue nutcracker and binding partner PI31 in Drosophila melanogaster models of Parkinson’s disease

Genome ◽  
2017 ◽  
Vol 60 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Eric M. Merzetti ◽  
Lindsay A. Dolomount ◽  
Brian E. Staveley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Severe Form ◽  
Altered Expression ◽  
Binding Partner ◽  
Locomotor Control ◽  
Dependent Model

Parkinsonian-pyramidal syndrome (PPS) is an early onset form of Parkinson’s disease (PD) that shows degeneration of the extrapyramidal region of the brain to result in a severe form of PD. The toxic protein build-up has been implicated in the onset of PPS. Protein removal is mediated by an intracellular proteasome complex: an E3 ubiquitin ligase, the targeting component, is essential for function. FBXO7 encodes the F-box component of the SCF E3 ubiquitin ligase linked to familial forms of PPS. The Drosophila melanogaster homologue nutcracker (ntc) and a binding partner, PI31, have been shown to be active in proteasome function. We show that altered expression of either ntc or PI31 in dopaminergic neurons leads to a decrease in longevity and locomotor ability, phenotypes both associated with models of PD. Furthermore, expression of ntc-RNAi in an established α-synuclein-dependent model of PD rescues the phenotypes of diminished longevity and locomotor control.

scholarly journals Genome Sequence of Acetobacter tropicalis DmPark25_167, a Bacterium Isolated from a Drosophila melanogaster Genetic Model of Parkinson’s Disease

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie A. Goddard ◽  
Samara C. Petersen ◽  
Gerald B. Call ◽  
John M. Chaston
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Genome Sequence ◽  
Bacterial Strain ◽  
Genetic Model ◽  
Type Iv Secretion ◽  
Methionine Metabolism ◽  
Content Type ◽  
Type Iv

ABSTRACT Here, we report the genome of Acetobacter tropicalis DmPark25_167, a bacterial strain isolated from a Drosophila melanogaster park25 mutant. The park25 mutant is an established genetic model of Parkinson’s disease. DmPark25_167 has duplicated methionine metabolism and type IV secretion gene alleles compared with another strain of A. tropicalis.

scholarly journals MYRICETIN ISOLATED FROM TURBINARIA ORNATA AMELIORATES ROTENONE INDUCED PARKINSONISM IN DROSOPHILA MELANOGASTER

2017 ◽  
Vol 9 (10) ◽  
pp. 39
Author(s):  
Vijayraja Dhanraj ◽  
Tamilarasan Manivasagam ◽  
Jeyaprakash Karuppaiah
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Dopaminergic Neurons ◽  
Fruit Flies ◽  
Neuroprotective Activity ◽  
Dopamine Level ◽  
Enzymatic Antioxidants ◽  
Turbinaria Ornata

Objective: Parkinson’s disease (PD) is a neurodegenerative disorder which affects the elderly population. Free radicals overproduction, oxidative stress, apoptosis, inflammation and abnormalities in mitochondria are critical mediators of the neuronal degeneration. In the present study neuroprotective activity of myricetin, a flavonoid isolated from brown seaweed Turbinaria ornata have been investigated in rotenone induced experimental PD models of Drosophila melanogaster.Methods: Male fruit flies (Drosophila melanogaster) were fed with an effective dose of 0.1% myricetin three hours before to the treatment with 500 µM of Rotenone (LD 50) for seven days and on 8th day through behavioral analysis the neuroprotective effect of myricetin was investigated for motor coordination in fruit flies. Lipid peroxidation was analyzed by estimating the levels of TBARS. Oxidative stress was determined by estimating the activities of enzymatic antioxidants superoxide dismutase, catalase, and glutathione peroxidase along with the level of reduced glutathione. Dopamine level was estimated in HPLC column detected at 280 nm with UV detectors and degree of apoptosis was studied apoptotic marker Bcl-2, Bax, caspases-3 and 9, cytochrome c and β-actin expressions in the whole body homogenate of fruit flies of experimental groups homogenized in 500μL of 0.1 M phosphate buffers (ice cold, pH, 7.4) containing 1 mmol EDTA.Results: Myricetin maintains the positive behavioral patterns against motor impairments due to the rotenone toxicity, it creates a balance in oxidant and antioxidant status, reduces the oxidative stress and inhibits apoptosis to retard neurodegeneration and maintains the dopamine level with a significant (p<0.05) difference compared to the rotenone treated group.Conclusion: The flavonoid myricetin by reducing the oxidative stress, maintaining the enzymatic antioxidants status and by inhibiting apoptosis prevents the degeneration of dopaminergic neurons. The dopaminergic neurons prevention reduces the depletion of dopamine and thereby promotes the muscular coordination and psychological well being of fruit flies of experimental group. Further in depth molecular level studies are in need to explore the preventive mechanisms of myricetin in Parkinson’s disease.

Pink1 suppresses α-synuclein-induced phenotypes in a Drosophila model of Parkinson’s disease

Genome ◽  
2008 ◽  
Vol 51 (12) ◽  
pp. 1040-1046 ◽  
Author(s):  
Amy M. Todd ◽  
Brian E. Staveley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Autosomal Recessive ◽  
Developmental Defects ◽  
Histological Studies ◽  
Progressive Loss ◽  
Drosophila Model ◽  
Climbing Ability ◽  
Protein Toxicity

Parkinson’s disease (PD) is the most prevalent human neurodegenerative movement disorder and is characterized by a selective and progressive loss of the dopaminergic neurons. Mutations in the genes parkin and PTEN-induced putative kinase 1 (PINK1) result in autosomal recessive forms of PD. It has been suggested that parkin and Pink1 function in the same pathway in Drosophila , with Pink1 acting upstream of parkin. Previous work in our laboratory has shown the ability of parkin to rescue an α-synuclein-induced PD-like phenotype in Drosophila. To investigate the ability of Pink1 to protect against α-synuclein-induced toxicity, we have performed longevity, mobility, and histological studies to determine whether Drosophila Pink1 can rescue the α-synuclein phenotypes. We have found that overexpression of Pink1 results in the rescue of the α-synuclein-induced phenotype of premature loss of climbing ability, suppression of degeneration of the ommatidial array, and the suppression of α-synuclein-induced developmental defects in the Drosophila eye. These results mark the first demonstration of Pink1 counteracting PD phenotypes in a protein toxicity animal model, and they show that Pink1 is able to impart protection against potentially harmful proteins such as α-synuclein that would otherwise result in cellular stress.

scholarly journals Evaluate the efficiency of resveratrol for treating Parkinson disease on Drosophila melanogaster model

2021 ◽  
Vol 5 (3) ◽  
pp. first
Author(s):  
Thao Thi Phuong Dang ◽  
Linh Mỹ Đào ◽  
Tươi Văn Phan ◽  
Anh Mẫn Huỳnh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Dopaminergic Neurons ◽  
Scientific Evidence ◽  
Life Quality ◽  
Antioxidant Compounds ◽  
Mobility Impairment ◽  
Disease Treatment ◽  
The Relationship

Parkinson's is the second most common neurodegenerative disease in the world (after Alzheimer's), characterized by the degeneration of dopaminergic neurons and mobility impairment, which consequently severely reduces patient life quality. Up to now, Parkinson's Disease cannot be completely cured. Base on the relationship between oxidative stress and the formation, the progression of Parkinson's Disease, antioxidant compounds have been studied as potential candidates in rescue or retard disease progression. Resveratrol is a strong antioxidant, anti-inflammatory, anti-apoptosis compound that exists in many fruits, especially grapes, strawberries..., and has activity depends on the used concentration. In this study, we evaluated the potential of resveratrol for treating Parkinson's Disease at concentrations of 0.064 mg/g, 0.32 mg/g, 0.64 mg/g by utilizing the knockdown dUCH (Drosophila ubiquitin carboxyl-terminal hydrolase) Drosophila melanogaster model. This model can mimic the typical symptoms of Parkinson's Disease and has been proved for the efficiency in screening drugs to treat the disease. Our results showed that the use of resveratrol at a concentration of 0.32 mg/g was effective in preventing the degeneration of dopaminergic neurons and improving mobility in dUCH knockdown flies. These results provided scientific evidence for the development of functional products or drugs to support Parkinson's Disease treatment.

scholarly journals Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1B9 Drosophila melanogaster Genetic Model of Parkinson’s Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110802 ◽  
Author(s):  
Simone Poddighe ◽  
Francescaelena De Rose ◽  
Roberto Marotta ◽  
Roberta Ruffilli ◽  
Maura Fanti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Genetic Model ◽  
Mucuna Pruriens ◽  
Velvet Bean

scholarly journals Protective effect of curcumin in transgenic Drosophila melanogaster model of Parkinson’s disease

2012 ◽  
Vol 2 (1) ◽  
pp. 3 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Gulshan Ara ◽  
Smita Jyoti ◽  
Mohammad Afzal
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Disease Model ◽  
Model Organisms ◽  
Cellular Processes ◽  
Normal Human ◽  
Climbing Ability ◽  
Dose Dependent

Studies on model organisms have been found to be invaluable in clarifying the cellular and molecular basis of normal cellular processes and disease pathogenesis. Drosophila mutants and transgenes have provided a platform to understand the mechanisms associated with degenerative disease. Studies on the role of polyphenols in protecting against neurodegenerative diseases are limited. In the present study, the effect of curcumin at various doses was studied on the climbing ability of the transgenic <em>Drosophila melanogaster </em>that expresses normal human α-synuclein in the neurons. A significant dose-dependent protection against loss of climbing ability was observed. The results suggest that curcumin can strongly improve the climbing ability of Parkinson’s disease model flies and also supports the utility of this model in studying the symptoms of Parkinson’s disease.

Sign in / Sign up

Export Citation Format

Share Document