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PEG-Enzyme for neurodegenerative diseases treatment

Zaghmi, Ahlem; Greschner, Andrea; Ramassamy, Charles; Gauthier, Marc A. . PEG-Enzyme for neurodegenerative diseases treatment In: Journée Phare 2016 (8e édition), 1-2 décembre 2016, Bromont (Québec).

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Résumé

Glutamate, as the major excitatory neurotransmitter in the central nervous system, is involved in many aspects of normal brain function including learning, memory and behavior (Campos-Peña et al., 2014, Hynd et al., 2004). During neurodegenerative diseases (Alzheimer’s disease, ...) the high levels of glutamate, induces excitotoxicity and leads to neuronal death and loss of cognitive function. Some studies have suggested that reducing blood levels of glutamate could induce efflux from the brain to the blood thereof leading to the decrease inthe cerebral concentrations (Boyko et al., 2014, Ruban et al., 2014).Our hypothesis is that the use of enzyme-polymer bio-conjugates could be interesting for the treatment of neurodegenerative diseases . The glutamate dehydrogenase (GDH) via its catalytic activity, will consume the excess glutamate and the biocompatible polymer selected, which is polyethylene glycol (PEG), will increase the duration of circulatory half-life.We propose, therefore, to synthesize conjugates GDH-PEG, to validate the maintenance of enzymatic activity and check their therapeutic efficacy.For this purpose, we conjugate PEG on the surface of the GDH (by using 2 ratios), we validate the reaction by visualization of our bio conjugates by SDS PAGE and by separating them with Size exclusion chromatography. After that we characterize the number of PEG per GDH by NMR and we evaluate the enzymatic activity before and after bio-conjugation. Our results demonstrate that the use of different Ratio allows us to have variable number of PEG grafted on the surface of our enzyme. After PEGylation, we showed that the enzyme activity is maintained.Currently, we are doing in vitro and in vivo tests in rat’s models to evaluate the effectiveness of the elimination of the excess toxic glutamate fromthe cerebrospinal fluid.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique no 93
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 11 mars 2019 15:54
Dernière modification: 11 mars 2019 15:54
URI: http://espace.inrs.ca/id/eprint/7897

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