Melatonin Increases Life Span, Restores the Locomotor Activity, and Reduces Lipid Peroxidation (LPO) in Transgenic Knockdown Parkin Drosophila melanogaster Exposed to Paraquat or Paraquat/Iron
| Autor: | Marlene Jimenez-Del-Rio, Hector Flavio Ortega-Arellano, Carlos Velez-Pardo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Paraquat
medicine.medical_specialty Iron Ubiquitin-Protein Ligases Longevity Biology Toxicology medicine.disease_cause Neuroprotection Parkin Antioxidants Lipid peroxidation Melatonin Animals Genetically Modified chemistry.chemical_compound Internal medicine Genetic model medicine Animals Drosophila Proteins General Neuroscience fungi Dopaminergic nervous system diseases Endocrinology Drosophila melanogaster chemistry Gene Knockdown Techniques Female Lipid Peroxidation Oxidative stress Locomotion medicine.drug |
| Zdroj: | Neurotoxicity research. 39(5) |
| ISSN: | 1476-3524 |
| Popis: | Parkinson’s disease (PD) is a complex progressive neurodegenerative disorder involving impairment of bodily movement caused by the specific destruction of dopaminergic (DAergic) neurons. Mounting evidence suggests that PD might be triggered by an interplay between environmental neurotoxicants (e.g., paraquat, PQ), heavy metals (e.g., iron), and gene alterations (e.g., PARKIN gene). Unfortunately, there are no therapies currently available that protect, slow, delay, or prevent the progression of PD. Melatonin (Mel, N-acetyl-5-methoxy tryptamine) is a natural hormone with pleiotropic functions including receptor-independent pathways which might be useful in the treatment of PD. Therefore, as a chemical molecule, it has been shown that Mel prolonged the lifespan and locomotor activity, and reduced lipid peroxidation (LPO) in wild-type Canton-S flies exposed to PQ, suggesting antioxidant and neuroprotective properties. However, it is not yet known whether Mel can protect or prevent the genetic model parkin deficient in flies against oxidative stress (OS) stimuli. Here, we show that Mel (0.5, 1, 3 mM) significantly extends the life span and locomotor activity of TH > parkin-RNAi/ + Drosophila melanogaster flies (> 15 days) compared to untreated flies. Knock-down (K-D) parkin flies treated with PQ (1 mM) or PQ (1 mM)/iron (1 mM) significantly diminished the survival index and climbing abilities (e.g., 50% of flies were dead and locomotor impairment by days 4 and 3, respectively). Remarkably, Mel reverted the noxious effect of PQ or PQ/iron combination in K-D parkin. Indeed, Mel protects TH > parkin-RNAi/ + Drosophila melanogaster flies against PQ- or PQ/iron-induced diminish survival, locomotor impairment, and LPO (e.g., 50% of flies were death and locomotor impairment by days 6 and 9, respectively). Similarly, Mel prevented K-D parkin flies against both PQ and PQ/iron. Taken together, these findings suggest that Mel can be safely used as an antioxidant and neuroprotectant agent against OS-stimuli in selective individuals at risk to suffer early-onset Parkinsonism and PD. |
| Databáze: | OpenAIRE |
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