title: Heat shock protein-70 (Hsp-70) suppresses paraquat-induced neurodegeneration by inhibiting JNK and caspase-3 activation in Drosophila model of Parkinson's disease.
abstract: Parkinson's disease (PD) is one of the most common neurodegenerative disorders with limited clinical interventions. A number of epidemiological as well as case-control studies have revealed an association between pesticide exposure, especially of paraquat (PQ) and occurrence of PD. Hsp70, a molecular chaperone by function, has been shown as one of the modulators of neurological disorders. However, paucity of information regarding the protective role of Hsp70 on PQ-induced PD like symptoms led us to hypothesize that modulation of hsp70 expression in the dopaminergic neurons would improve the health of these cells. We took advantage of Drosophila, which is a well-established model for neurological research and also possesses genetic tools for easy manipulation of gene expression with limited ethical concern. Over-expression of hsp70 was found to reduce PQ-induced oxidative stress along with JNK and caspase-3 mediated dopaminergic neuronal cell death in exposed organism. Further, anti-apoptotic effect of hsp70 was shown to confer better homeostasis in the dopaminergic neurons of PQ-exposed organism as evidenced by their improved locomotor performance and survival. The study has merit in the context of human concern since we observed protection of dopaminergic neurons in PQ-exposed organism by over-expressing a human homologue of hsp70, HSPA1L, in these cells. The effect was parallel to that observed with Drosophila hsp70. These findings reflect the potential therapeutic applicability of hsp70 against PQ-induced PD like symptoms in an organism.
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Shukla
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Pragya
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Hitesh Singh
authors.initials: HS
authors.lastname: Chaouhan
authors.affiliation: School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, Gujrat, India.
authors.forename: Anand Krishna
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Analytical Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
authors.forename: Devendra Kumar
authors.initials: DK
authors.lastname: Patel
authors.affiliation: Department of Biotechnology, Jamia Hamdard, New Delhi, India.
authors.forename: Malik Zainul
authors.initials: MZ
authors.lastname: Abdin
authors.affiliation: Embryotoxicology Section, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
authors.forename: Debapratim Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010269:Paraquat / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D010269:Paraquat