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TitlePhospholipase D functional ablation has a protective effect in an Alzheimer's disease Caenorhabditis elegans model
Author(s)Bravo, Francisca Vaz
Da Silva, Jorge
Chan, Robin Barry
Di Paolo, Gilbert
Teixeira-Castro, Andreia
Oliveira, Tiago Gil
Issue date23-Feb-2018
PublisherNature Publishing Group
JournalScientific Reports
Abstract(s)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.
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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