Aza-Flavanone Diminishes Parkinsonism in the Drosophila melanogaster Parkin Mutant.

Parkinson's disease is a chronic and progressive neurodegenerative disease, induced by slow and progressive death of the dopaminergic (DA) neurons from the midbrain region called substantia nigra (SNc) leading to difficulty in locomotion. At present, very few potential therapeutic drugs are available for treatment, necessitating an urgent need for development. In the current study, the parkin transgenic Drosophila melanogaster model that induces selective loss in dopaminergic neurons and impairment of locomotory functions has been used to see the effect of the aza-flavanone molecule. D. melanogaster serves as an amazing in vivo model making valuable contribution in the development of promising treatment strategies. Our in-silico study showed spontaneous binding of this molecule to the D2 receptor making it a potential dopamine agonist. PARKIN protein is well conserved, and it has been reported that Drosophila PARKIN is 42% identical to human PARKIN. Interestingly, this molecule enhances the motor coordination and survivability rate of the transgenic flies along with an increase in expression of the master regulator of Dopamine synthesis, that is, tyrosine hydroxylase (TH), in the substantia nigra region of the fly brain. Moreover, it plays a significant effect on mitochondrial health and biogenesis via modulation of a conserved mitochondrial protein PHB2. Therefore, this molecule could lead to the development of an effective therapeutic approach for the treatment of PD.

Citation

Chitrakshi Pant, Moumita Chakrabarti, Jolly Janette Mendonza, Bogonda Ganganna, Srihari Pabbaraja, Manika Pal Bhadra. Aza-Flavanone Diminishes Parkinsonism in the Drosophila melanogaster Parkin Mutant. ACS chemical neuroscience. 2021 Dec 01;12(23):4380-4392

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PMID: 34763419

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