Characterizing dopaminergic neuron vulnerability using genome-wide analysis

Using Drosophila, Davis et al. identify novel factors that render dopaminergic neurons vulnerable to degeneration. As dopaminergic neurons are selectively vulnerable in Parkinson’s Disease, these results provide insight into the development of potential therapeutic targets to protect these vulnerabl...

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Bibliographic Details
Published in:Genetics (Austin) 2021-08, Vol.218 (4)
Main Authors: Davis, Jacinta, Da Silva Santos, Claire, Zavala, Narda Caudillo, Gans, Nicholas, Patracuolla, Daniel, Fehrenbach, Monica, Babcock, Daniel T
Format: Article
Language:English
Subjects:
Animals
Dopamine receptors
Dopaminergic Neurons - metabolism
Dopaminergic Neurons - physiology
Drosophila melanogaster
Fruit flies
Genes
Genetics
Genome, Insect
Genomes
Insects
Locomotion
Movement disorders
Mutants
Neurodegenerative diseases
Neurogenetics
Neurons
Nucleotides
Parkinson Disease - genetics
Parkinson's disease
Polymorphism, Single Nucleotide
Single-nucleotide polymorphism
Tissue analysis
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Summary:Using Drosophila, Davis et al. identify novel factors that render dopaminergic neurons vulnerable to degeneration. As dopaminergic neurons are selectively vulnerable in Parkinson’s Disease, these results provide insight into the development of potential therapeutic targets to protect these vulnerable neuronal populations. Abstract Parkinson’s disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1093/genetics/iyab081