1. Heat shock protein-70 (Hsp-70) suppresses paraquat-induced neurodegeneration by inhibiting JNK and caspase-3 activation in Drosophila model of Parkinson's disease.
- Author
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Shukla AK, Pragya P, Chaouhan HS, Tiwari AK, Patel DK, Abdin MZ, and Chowdhuri DK
- Subjects
- Animals, Apoptosis drug effects, Apoptosis genetics, Disease Models, Animal, Dopaminergic Neurons drug effects, Dopaminergic Neurons enzymology, Drosophila Proteins metabolism, Drosophila melanogaster drug effects, Drosophila melanogaster enzymology, Drosophila melanogaster genetics, Drosophila melanogaster physiology, HSP70 Heat-Shock Proteins genetics, Motor Activity drug effects, Motor Activity genetics, Oxidative Stress drug effects, Oxidative Stress genetics, Paraquat toxicity, Parkinsonian Disorders etiology, Parkinsonian Disorders genetics, Up-Regulation, Caspase 3 metabolism, Dopaminergic Neurons metabolism, HSP70 Heat-Shock Proteins metabolism, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Parkinsonian Disorders therapy
- 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.
- Published
- 2014
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