Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model

Abstract Phospholipase D (PLD) is a key player in the modulation of multiple aspects of cell physiology and has been proposed as a therapeutic target for Alzheimer’s disease (AD). Here, we characterize a PLD mutant, pld-1, using the Caenorhabditis elegans animal model. We show that pld-1 animals pre...

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Autores principales:	Francisca Vaz Bravo, Jorge Da Silva, Robin Barry Chan, Gilbert Di Paolo, Andreia Teixeira-Castro, Tiago Gil Oliveira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/adc50c1c0cbe438192dca4a769e19623
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spelling	oai:doaj.org-article:adc50c1c0cbe438192dca4a769e196232021-12-02T16:07:52ZPhospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model10.1038/s41598-018-21918-52045-2322https://doaj.org/article/adc50c1c0cbe438192dca4a769e196232018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21918-5https://doaj.org/toc/2045-2322Abstract Phospholipase D (PLD) is a key player in the modulation of multiple aspects of cell physiology and has been proposed as a therapeutic target for Alzheimer’s disease (AD). Here, we characterize a PLD mutant, pld-1, using the Caenorhabditis elegans animal model. We show that pld-1 animals present decreased phosphatidic acid levels, that PLD is the only source of total PLD activity and that pld-1 animals are more sensitive to the acute effects of ethanol. We further show that PLD is not essential for survival or for the normal performance in a battery of behavioral tests. Interestingly, pld-1 animals present both increased size and lipid stores levels. While ablation of PLD has no important effect in worm behavior, its ablation in an AD-like model that overexpresses amyloid-beta (Aβ), markedly improves various phenotypes such as motor tasks, prevents susceptibility to a proconvulsivant drug, has a protective effect upon serotonin treatment and reverts the biometric changes in the Aβ animals, leading to the normalization of the worm body size. Overall, this work proposes the C. elegans model as a relevant tool to study the functions of PLD and further supports the notion that PLD has a significant role in neurodegeneration.Francisca Vaz BravoJorge Da SilvaRobin Barry ChanGilbert Di PaoloAndreia Teixeira-CastroTiago Gil OliveiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francisca Vaz Bravo Jorge Da Silva Robin Barry Chan Gilbert Di Paolo Andreia Teixeira-Castro Tiago Gil Oliveira Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
description	Abstract Phospholipase D (PLD) is a key player in the modulation of multiple aspects of cell physiology and has been proposed as a therapeutic target for Alzheimer’s disease (AD). Here, we characterize a PLD mutant, pld-1, using the Caenorhabditis elegans animal model. We show that pld-1 animals present decreased phosphatidic acid levels, that PLD is the only source of total PLD activity and that pld-1 animals are more sensitive to the acute effects of ethanol. We further show that PLD is not essential for survival or for the normal performance in a battery of behavioral tests. Interestingly, pld-1 animals present both increased size and lipid stores levels. While ablation of PLD has no important effect in worm behavior, its ablation in an AD-like model that overexpresses amyloid-beta (Aβ), markedly improves various phenotypes such as motor tasks, prevents susceptibility to a proconvulsivant drug, has a protective effect upon serotonin treatment and reverts the biometric changes in the Aβ animals, leading to the normalization of the worm body size. Overall, this work proposes the C. elegans model as a relevant tool to study the functions of PLD and further supports the notion that PLD has a significant role in neurodegeneration.
format	article
author	Francisca Vaz Bravo Jorge Da Silva Robin Barry Chan Gilbert Di Paolo Andreia Teixeira-Castro Tiago Gil Oliveira
author_facet	Francisca Vaz Bravo Jorge Da Silva Robin Barry Chan Gilbert Di Paolo Andreia Teixeira-Castro Tiago Gil Oliveira
author_sort	Francisca Vaz Bravo
title	Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
title_short	Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
title_full	Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
title_fullStr	Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
title_full_unstemmed	Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model
title_sort	phospholipase d functional ablation has a protective effect in an alzheimer’s disease caenorhabditis elegans model
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/adc50c1c0cbe438192dca4a769e19623
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Phospholipase D functional ablation has a protective effect in an Alzheimer’s disease Caenorhabditis elegans model

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