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

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.

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Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster

Antioxidants ◽

10.3390/antiox9010052 ◽

2020 ◽

Vol 9 (1) ◽

pp. 52 ◽

Cited By ~ 1

Author(s):

Federica De Lazzari ◽

Federica Sandrelli ◽

Alexander J. Whitworth ◽

Marco Bisaglia

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Drosophila Melanogaster ◽

Therapeutic Potential ◽

Experimental System ◽

Rapid Screening ◽

Antioxidant Compounds ◽

Oxygen Species ◽

Protective Effects ◽

High Concentrations

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson’s disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal’s rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments.

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

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i11.19931 ◽

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.

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Curcumin Effectively Rescued Parkinson’s Disease-Like Phenotypes in a Novel Drosophila melanogaster Model with dUCH Knockdown

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2038267 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 19

Author(s):

Thi Thanh Nguyen ◽

My Dung Vuu ◽

Man Anh Huynh ◽

Masamitsu Yamaguchi ◽

Linh Thuoc Tran ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Genetic Factors ◽

Neurodegenerative Disorder ◽

Appropriate Therapy ◽

Genetic And Environmental Factors ◽

The Relationship ◽

Common Neurodegenerative Disorder

The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson’s disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.

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

Genome ◽

10.1139/gen-2016-0069 ◽

2017 ◽

Vol 60 (1) ◽

pp. 1-7 ◽

Cited By ~ 6

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.

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

Genome ◽

10.1139/g06-011 ◽

2006 ◽

Vol 49 (5) ◽

pp. 505-510 ◽

Cited By ~ 21

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.

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FGF, Mechanism of Action, Role in Parkinson’s Disease, and Therapeutics

Frontiers in Pharmacology ◽

10.3389/fphar.2021.675725 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yiqiu Liu ◽

Junyu Deng ◽

Ye Liu ◽

Wei Li ◽

Xuqiang Nie

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Dopaminergic Neurons ◽

Lewy Body ◽

Psychiatric Symptoms ◽

Life Quality ◽

Pathological Process ◽

Muscle Stiffness ◽

Motor Dysfunction

Parkinson’s disease (PD) is a neurodegenerative disease associated with severe disability and adverse effects on life quality. In PD, motor dysfunction can occur, such as quiescence, muscle stiffness, and postural instability. PD is also associated with autonomic nervous dysfunction, sleep disorders, psychiatric symptoms, and other non-motor symptoms. Degeneration of dopaminergic neurons in the substantia nigra compact (SNPC), Lewy body, and neuroinflammation are the main pathological features of PD. The death or dysfunction of dopaminergic neurons in the dense part of the substantia nigra leads to dopamine deficiency in the basal ganglia and motor dysfunction. The formation of the Lewy body is associated with the misfolding of α-synuclein, which becomes insoluble and abnormally aggregated. Astrocytes and microglia mainly cause neuroinflammation, and the activation of a variety of pro-inflammatory transcription factors and regulatory proteins leads to the degeneration of dopaminergic neurons. At present, PD is mainly treated with drugs that increase dopamine concentration or directly stimulate dopamine receptors. Fibroblast growth factor (FGF) is a family of cellular signaling proteins strongly associated with neurodegenerative diseases such as PD. FGF and its receptor (FGFR) play an essential role in the development and maintenance of the nervous system as well as in neuroinflammation and have been shown to improve the survival rate of dopaminergic neurons. This paper summarized the mechanism of FGF and its receptors in the pathological process of PD and related signaling pathways, involving the development and protection of dopaminergic neurons in SNPC, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. It provides a reference for developing drugs to slow down or prevent the potential of PD.

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Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson’s Disease

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.644776 ◽

2021 ◽

Vol 15 ◽

Author(s):

Kathleen Carmichael ◽

Rebekah C. Evans ◽

Elena Lopez ◽

Lixin Sun ◽

Mantosh Kumar ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Distinct Group ◽

Disease Treatment ◽

Different Populations ◽

Brain Circuit ◽

Chemical Messenger ◽

Reward Motivation ◽

The Brain

Dopamine is an important chemical messenger in the brain, which modulates movement, reward, motivation, and memory. Different populations of neurons can produce and release dopamine in the brain and regulate different behaviors. Here we focus our discussion on a small but distinct group of dopamine-producing neurons, which display the most profound loss in the ventral substantia nigra pas compacta of patients with Parkinson’s disease. This group of dopaminergic neurons can be readily identified by a selective expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and accounts for 70% of total nigrostriatal dopaminergic neurons in both human and mouse brains. Recently, we presented the first whole-brain circuit map of these ALDH1A1-positive dopaminergic neurons and reveal an essential physiological function of these neurons in regulating the vigor of movement during the acquisition of motor skills. In this review, we first summarize previous findings of ALDH1A1-positive nigrostriatal dopaminergic neurons and their connectivity and functionality, and then provide perspectives on how the activity of ALDH1A1-positive nigrostriatal dopaminergic neurons is regulated through integrating diverse presynaptic inputs and its implications for potential Parkinson’s disease treatment.

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