Étude du lien fonctionnel entre Neural Plakophilin-Related Armadillo Protein, Préséniline 1, Synaptophysine et Butyrylcholinestérase dans le contexte de la maladie d'Alzheimer

Authors: Mendonça Marchini Blois, Anne
Advisor: Lévesque, Georges
Abstract: Alzheimer’s disease (AD) is characterized by synaptic and neuronal loss. The presence of mutations on the Presenilin 1 (PS1) gene are associated with a very aggressive form of AD and these mutations could amplify the synaptic and neuronal loss. AD is also characterized by the increase in Butyrylcholinestérase protein (BuChE) which plays a role in acetylcholine (ACh) degradation. Moreover, ACh is decreased in AD. Synaptophysin protein (Syn), a marker of synaptogenesis has also been shown to be decreased in AD. Prior studies in the laboratory demonstrated an interaction between PS1 andNeural-Plakophilin-Related Armadillo Protein (NPRAP), a neuronal protein whose gene deletion causes important cognitive dysfunctions. Previous work has shown that NPRAP modulates expression of BuChE gene and seems to be involved in Syn expression. Furthermore, we identified a mutation in NPRAP’s gene that could be associated with the development of AD.My hypothesis is that PS1 and NPRAP are important for the maintenance of neuronal integrity, via Syn and BuChE. My objective was to study the effect of the wild-type and mutated form of PS1 and NPRAP (PS1 L392V / PS1 M146L / NPRAP G810R) on the modulation of Syn and BuChE’s levels. Syn and BuChE’s expression were analysed at the protein level and ARNm level in HEK-293 and SH-SY5Y cells. We also verified Syn and BuChE expression at the cellular level by Immunofluorescence. The results obtained seems to indicate an increase of the level of BuChE in SH-SY5Y transfected cells by PS1-M146L and NPRAP sauvage. There is no significant variation of Syn level and immunofluorescence analysis were not conclusive. Other experiments will be necessary to verify the impact of PS1 M146L and NPRAP sauvage on the expression of BuChE’s.
Document Type: Mémoire de maîtrise
Issue Date: 2018
Open Access Date: 17 April 2019
Permalink: http://hdl.handle.net/20.500.11794/34479
Grantor: Université Laval
Collection:Thèses et mémoires

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