title: Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons in Drosophila model of Parkinson's disease.
abstract: parkin loss associated early-onset of Parkinson's disease, involves mitochondrial dysfunction and oxidative stress as the plausible decisive molecular mechanisms in disease pathogenesis. Mitochondrial dysfunction involves several up/down regulation of gene products, one of which being p53 is found to be elevated. Elevated p53 is involved in mitochondrial mediated apoptosis of neuronal cells in Parkinson's patients who are folate deficient as well. The present study therefore attempts to examine the effect of Folic acid (FA) supplementation in alleviation of anomalies associated with parkin knockdown using RNAi approach, specific to Dopaminergic (DA) neurons in Drosophila model system. Here we show that FA supplementation provide protection against parkin RNAi associated discrepancies, thereby improves locomotor ability, reduces mortality and oxidative stress, and partially improves Zn levels. Further, metabolic active cell status and ATP levels were also found to be improved thereby indicating improved mitochondrial function. To corroborate FA supplementation in mitochondrial functioning further, status of p53 and spargel was checked by qRT-PCR. Here we show that folic acid supplementation enrich mitochondrial functioning as depicted from improved spargel level and lowered p53 level, which was originally vice versa in parkin knockdown flies cultured in standard media. Our data thus support the potential of folic acid in alleviating the behavioural defects, oxidative stress, augmentation of zinc and ATP levels in parkin knock down flies. Further, folic acid role in repressing mitochondrial dysfunction is encouraging to further explore its possible mechanistic role to be utilized as potential therapeutics for Parkinson's disease.
authors.affiliation: Cell and Neurobiology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Srivastav
authors.affiliation: Cell and Neurobiology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Cell and Neurobiology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, India.
authors.forename: Amarish Kumar
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Cell and Neurobiology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, India. Electronic address: skrishna@bhu.ac.in.
authors.forename: Saripella
authors.initials: S
authors.lastname: Srikrishna
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005492:Folic Acid / Q000008:administration & dosage*; D055785:Gene Knockdown Techniques; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059326:Serotonergic Neurons / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D005492:Folic Acid; D044767:Ubiquitin-Protein Ligases; C487430:park protein, Drosophila
keywords: Dopaminergic and serotonergic neurons; Folic acid; Oxidative stress; p53; parkin; spargel