Folic Acid Supplementation Ameliorates Oxidative Stress, Metabolic Functions and Developmental Anomalies in a Novel Fly Model of Parkinson’s Disease

Mutations in parkin cause early-onset Parkinson’s disease. Studies involving Drosophila model have emphasised mitochondrial dysfunction as a critical event in disease pathogenesis. In this context, we employed a novel recessive allele of parkin, park c00062 , for the current study. The piggyBac insertion at 3rd intron of parkin in park c00062 was confirmed by PCR. Homozygous park c00062 has diminished levels of truncated parkin transcript with no detectable protein as confirmed by qRT-PCR and western blot analysis, respectively. The homozygous park c00062 displayed severe developmental anomalies involving reduced body size, ~45 % pupal lethality, high mortality with locomotory defect, elevated oxidative stress, low metabolic active cell status with low mitochondrial respiration as reflected from reduced ATP levels. Further, folic acid therapeutic potential was analysed in park c00062 . Here we show that dietary folic acid provided protection against disparities involving pupal lethality, high mortality, locomotory defect, elevated oxidative stress and low metabolic active cell status associated with park c00062 . Further mitochondrial respiration was enhanced as reflected from improved ATP levels in folate supplemented park c00062 . To corroborate mitochondrial functioning further our analysis regarding transcript status of p53 and spargel by qRT-PCR, revealed down regulation of p53 and up regulation of spargel in folate supplemented park c00062 , which was originally vice a versa. Our data thus support the potential of FA in alleviating the disparities associated with parkin loss of function in fly model. Further, FA role in alleviating mitochondrial dysfunction is encouraging to further explore FA mechanistic role to be utilized as potential therapeutics for parkin mediated neurodegenerative diseases.