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Characterizing dopaminergic neuron vulnerability using genome-wide analysis

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 Dro...

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Autores principales: Davis, Jacinta, Da Silva Santos, Claire, Zavala, Narda Caudillo, Gans, Nicholas, Patracuolla, Daniel, Fehrenbach, Monica, Babcock, Daniel T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864742/
https://www.ncbi.nlm.nih.gov/pubmed/34038543
http://dx.doi.org/10.1093/genetics/iyab081
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author Davis, Jacinta
Da Silva Santos, Claire
Zavala, Narda Caudillo
Gans, Nicholas
Patracuolla, Daniel
Fehrenbach, Monica
Babcock, Daniel T
author_facet Davis, Jacinta
Da Silva Santos, Claire
Zavala, Narda Caudillo
Gans, Nicholas
Patracuolla, Daniel
Fehrenbach, Monica
Babcock, Daniel T
author_sort Davis, Jacinta
collection PubMed
description 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.
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spelling pubmed-88647422022-02-24 Characterizing dopaminergic neuron vulnerability using genome-wide analysis Davis, Jacinta Da Silva Santos, Claire Zavala, Narda Caudillo Gans, Nicholas Patracuolla, Daniel Fehrenbach, Monica Babcock, Daniel T Genetics Neurogenetics 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. Oxford University Press 2021-05-26 /pmc/articles/PMC8864742/ /pubmed/34038543 http://dx.doi.org/10.1093/genetics/iyab081 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Neurogenetics
Davis, Jacinta
Da Silva Santos, Claire
Zavala, Narda Caudillo
Gans, Nicholas
Patracuolla, Daniel
Fehrenbach, Monica
Babcock, Daniel T
Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title_full Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title_fullStr Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title_full_unstemmed Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title_short Characterizing dopaminergic neuron vulnerability using genome-wide analysis
title_sort characterizing dopaminergic neuron vulnerability using genome-wide analysis
topic Neurogenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864742/
https://www.ncbi.nlm.nih.gov/pubmed/34038543
http://dx.doi.org/10.1093/genetics/iyab081
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