Protective mechanism of Wnt4 gene on Parkinson’s disease (PD) transgenic Drosophila

The objective of this study was to explore the neuroprotective effect of moxibustion on rats with Parkinson’s disease (PD) and its mechanism. A Parkinson’s disease model was established in rats using a two-point stereotactic 6-hydroxydopamine injection in the right substantia nigra (SN) and ventral tegmental area. The rats received moxibustion at the Baihui (GV20) and Sishencong (EX-HN1) acupoints for 20 minutes, six times a week, for 6 weeks. The right SN tissue was histologically and immunohistochemically examined. Differentially expressed genes (DEGs) were identified through RNA sequencing. In addition, the levels of tyrosine hydroxylase (TH), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in SN were measured. In comparison to the model group, the moxibustion group showed a significantly greater TH immunoreactivity and a higher behavioural score. In particular, moxibustion led to an increase in the number and morphological stability of SN neural cells. The functional pathway analysis showed that DEGs are closely related to the ferroptosis pathway. GPX4 and FTH1 in the SN were significantly overexpressed in the moxibustion-treated rats with PD. Moxibustion can effectively reduce the death of SN neurons, decrease the occurrence of ferroptosis, and increase the TH activity to protect the neurons in rats with PD. The protective mechanism may be associated with suppression of the ferroptosis.

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Effect of Cabergoline on Cognitive Impairments in Transgenic Drosophila Model of Parkinson’s Disease

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200514100917 ◽

2020 ◽

Vol 17 (10) ◽

pp. 1261-1269

Author(s):

Yasir Hasan Siddique ◽

Rahul ◽

Mantasha Idrisi ◽

Mohd. Shahid

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Neurodegenerative Disorder ◽

Cognitive Impairments ◽

Alpha Synuclein ◽

Substantia Nigra Pars Compacta ◽

Positive Interaction ◽

Drosophila Model ◽

Transgenic Drosophila

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.

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Lemon grass extract alleviates oxidative stress and delayed the loss of climbing ability in transgenic Drosophila model of Parkinson’s disease

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210413141434 ◽

2021 ◽

Vol 18 ◽

Author(s):

Yasir Hasan Siddique ◽

Falaq Naz ◽

Mantasha I. ◽

M. Shahid

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Alpha Synuclein ◽

Substantia Nigra Pars Compacta ◽

Positive Interaction ◽

Lemon Grass ◽

Drosophila Model ◽

Climbing Ability ◽

Transgenic Drosophila

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.

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