Neurodegeneration and locomotor dysfunction in Drosophila scarlet mutants
| Autor: | Barry Ganetzky, Katherine Waldeck, Daniel T. Babcock, Patrick C. Cunningham |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Kynurenine pathway Neurodegeneration Dopaminergic Cell Biology Biology medicine.disease Free radical scavenger Eye pigmentation Neuroprotection 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Kynurenic acid chemistry medicine Neuroscience Kynurenine |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons, resulting in progressive locomotor dysfunction. Identification of genes required for the maintenance of these neurons should help to identify potential therapeutic targets. However, little is known regarding the factors that render dopaminergic neurons selectively vulnerable to PD. Here we show that Drosophila melanogaster scarlet mutants exhibit an age-dependent progressive loss of dopaminergic neurons, along with subsequent locomotor defects and a shortened lifespan. Knockdown of Scarlet specifically within dopaminergic neurons is sufficient to produce this neurodegeneration, demonstrating a unique role for Scarlet beyond its well-characterized role in eye pigmentation. Both genetic and pharmacological manipulation of the kynurenine pathway rescued loss of dopaminergic neurons by promoting synthesis of the free radical scavenger Kynurenic Acid (KYNA) and limiting the production of the free radical generator 3-hydroxykynurenine (3-HK). Finally, we show that expression of wild-type Scarlet is neuroprotective in a model of PD, suggesting that manipulating kynurenine metabolism may be a potential therapeutic option in treating PD. |
| Databáze: | OpenAIRE |
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