Neurodegeneration and locomotor dysfunction in Drosophila scarlet mutants

Journal of Cell Science
Patrick C CunninghamDaniel T Babcock

Abstract

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.This article has an a...Continue Reading

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Citations

May 16, 2020·Journal of Oncology·Emily L PatonIsabel R Schlaepfer
Aug 28, 2020·Frontiers in Physiology·Aleksandr V ZhuravlevElena V Savvateeva-Popova
Dec 22, 2020·Genesis : the Journal of Genetics and Development·Nur Izzatur Binti IsmailHajime Watanabe
May 27, 2021·Genetics·Jacinta DavisDaniel T Babcock
Jan 15, 2022·Molecular Neurobiology·Aleksandr V ZhuravlevElena V Savvateeva-Popova

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