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Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin

Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer's disease (FAD). Using the Drosophila centr...

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Autores principales: Michno, Kinga, Knight, David, Campussano, Jorge M., van de Hoef, Diana, Boulianne, Gabrielle L.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733141/
https://www.ncbi.nlm.nih.gov/pubmed/19730737
http://dx.doi.org/10.1371/journal.pone.0006904
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author Michno, Kinga
Knight, David
Campussano, Jorge M.
van de Hoef, Diana
Boulianne, Gabrielle L.
author_facet Michno, Kinga
Knight, David
Campussano, Jorge M.
van de Hoef, Diana
Boulianne, Gabrielle L.
author_sort Michno, Kinga
collection PubMed
description Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer's disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer's disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation.
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spelling pubmed-27331412009-09-04 Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin Michno, Kinga Knight, David Campussano, Jorge M. van de Hoef, Diana Boulianne, Gabrielle L. PLoS One Research Article Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer's disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer's disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation. Public Library of Science 2009-09-04 /pmc/articles/PMC2733141/ /pubmed/19730737 http://dx.doi.org/10.1371/journal.pone.0006904 Text en Michno et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Michno, Kinga
Knight, David
Campussano, Jorge M.
van de Hoef, Diana
Boulianne, Gabrielle L.
Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title_full Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title_fullStr Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title_full_unstemmed Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title_short Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin
title_sort intracellular calcium deficits in drosophila cholinergic neurons expressing wild type or fad-mutant presenilin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733141/
https://www.ncbi.nlm.nih.gov/pubmed/19730737
http://dx.doi.org/10.1371/journal.pone.0006904
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