scholarly journals Effect of Majun Baladur on life span, climbing ability, oxidative stress and dopaminergic neurons in the transgenic Drosophila model of Parkinson's disease

Heliyon ◽  
2019 ◽  
Vol 5 (4) ◽  
pp. e01483
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Rahul ◽  
Mohammad Rashid ◽  
Tajuddin
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Mantasha I. ◽  
M. Shahid

Background: Parkinson’s Disease (PD) is characterized by the aggregation of α-synuclein, formation of Lewy bodies and the selective loss of dopaminergic neurons of mesencephalic substantia nigra pars compacta (SNC) with the debilitating motor symptoms. Introduction: The available treatment for PD provides symptomatic relief with no control on the progression of the disease. The treatment is also associated with several side effects. As the neurodegeneration in PD is also associated with the oxidative stress, antioxidants from plants could play an important role in reducing the PD symptoms. With this aim we decided to study the effect of Lemon grass extract (LGE) on the transgenic Drosophila model of PD expressing human alpha synuclein in the neurons. Methods: The PD flies allowed were allowed to feed on different doses of LGE established in diet for 24 days and then assayed for climbing ability and oxidative stress markers. The molecular docking study was also performed for citral (the component of the extract) and human α-synuclein. Results and discussion: A dose dependent significant improvement in the climbing ability and reduction in oxidative stress was observed in the PD flies exposed to LGE. In our earlier study on LGE, citral was found to be the main component of the extract by GC-MS analysis. The docking results also support the positive interaction between citral and human α-synuclein. Conclusion: The results suggests that LGE is potemnt in reducing the PD symptoms being mimicked in transgenic Drosophila.


2020 ◽  
Vol 07 ◽  
Author(s):  
Yasir Hasan Siddique ◽  
Falaq Naz ◽  
Mohammad Rashid

Aim: The effect of Majun Falasfa (MF) was studied on the transgenic Drosophila expressing human alpha synuclein panneurally. Background: MF is a Unani medicine used for enhancing mental power and treating kidney, joint pains and urinary tract diseases. It is also use for phlegmatic diseases. It is also being used in age related dementia and to counter the effects of ageing. Methods: The equivalents of recommended dose for human were established for 20g of fly food i.e. 0.0014, 0.0028, 0.0042 and 0.0056g per 20g of diet. The PD flies were allowed to feed on it for 24 days before studying its effect on cognitive and oxidative stress parameters. Immunohistochemistry was also performed study the effect of MF on human alpha synuclein expression. Results: The exposure to MF increased the life span and improves the activity of PD flies. MF delayed the loss of climbing ability of PD flies. The exposure of PD flies to MF significantly reduced the oxidative stress and improves the antioxidant enzymes homeostasis compared to unexposed PD flies. The exposure to MF reduces the formation of Lewy bodies as is evident by immunohistochemistry. Conclusion: MF is potent in reducing the PD (Parkinson’s disease) symptoms being mimicked in the transgenic flies.


2020 ◽  
Vol 17 (10) ◽  
pp. 1261-1269
Author(s):  
Yasir Hasan Siddique ◽  
Rahul ◽  
Mantasha Idrisi ◽  
Mohd. Shahid

Background: Parkinson’s disease is a common neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Introduction: The effects of alpha synuclein, parkin mutation and pharmacological agents have been studied in the Drosophila model. Methods: The effect of cabergoline was studied on the cognitive impairments exhibited by the transgenic Drosophila expressing human alpha-synuclein in the neurons. The PD flies were allowed to feed on the diet having 0.5, 1 and 1.5 μM of cabergoline. Results and Discussion: The exposure of cabergoline not only showed a dose-dependent significant delay in the cognitive impairments but also prevented the loss of dopaminergic neurons. Molecular docking studies showed the positive interaction between cabergoline and alpha-synuclein. Conclusion: The results suggest a protective effect of cabergoline against the cognitive impairments.


Genome ◽  
2008 ◽  
Vol 51 (12) ◽  
pp. 1040-1046 ◽  
Author(s):  
Amy M. Todd ◽  
Brian E. Staveley

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.


Genome ◽  
2017 ◽  
Vol 60 (1) ◽  
pp. 1-7 ◽  
Author(s):  
P. Githure M’Angale ◽  
Brian E. Staveley

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Sun ◽  
Zhe-Xu Ding ◽  
Xin Luo ◽  
Qing-Shan Liu ◽  
Yong Cheng

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.


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