title: Ida-1, the Caenorhabditis elegans orthologue of mammalian diabetes autoantigen IA-2, potentially acts as a common modulator between Parkinson's disease and Diabetes: role of Daf-2/Daf-16 insulin like signalling pathway.
abstract: The lack of cure to age associated Parkinson's disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing "human" alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes.
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Soobiya
authors.initials: S
authors.lastname: Fatima
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jadiya
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.lastname: Shamsuzzama
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Aamir
authors.initials: A
authors.lastname: Nazir
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D051844:alpha-Synuclein; C108831:daf-16 protein, C elegans; D049452:Green Fluorescent Proteins; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C418215:IDA-1 protein, C elegans; D017027:Protein Tyrosine Phosphatases