Stabilization of Human Tyrosine Hydroxylase ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Stabilization of Human Tyrosine Hydroxylase in Maltodextrin Nanoparticles for Delivery to Neuronal Cells and Tissue
Auteur(s) :
Bezem, Maria T. [Auteur]
Johannessen, Fredrik G. [Auteur]
Jung Kunwar, K. C. [Auteur]
Gundersen, Edvin Tang [Auteur]
Jorge-Finnigan, Ana [Auteur]
Ying, Ming [Auteur]
Betbeder, Didier [Auteur]
498252|||Lille Inflammation Research International Center - U 995 [LIRIC]
Université d'Artois [UA]
Herfindal, Lars [Auteur]
Martinez, Aurora [Auteur]
Johannessen, Fredrik G. [Auteur]
Jung Kunwar, K. C. [Auteur]
Gundersen, Edvin Tang [Auteur]
Jorge-Finnigan, Ana [Auteur]
Ying, Ming [Auteur]
Betbeder, Didier [Auteur]
498252|||Lille Inflammation Research International Center - U 995 [LIRIC]
Université d'Artois [UA]
Herfindal, Lars [Auteur]
Martinez, Aurora [Auteur]
Titre de la revue :
Bioconjugate Chemistry
Nom court de la revue :
Bioconjugate Chem.
Numéro :
29
Pagination :
493-502
Date de publication :
2018-02-01
ISSN :
1043-1802
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but ERT has been less successful for the correction of disorders with neurological manifestations. ...
Lire la suite >Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but ERT has been less successful for the correction of disorders with neurological manifestations. In this work, we have tested the functionality of nanoparticles (NP) composed of maltodextrin with a lipid core to bind and stabilize tyrosine hydroxylase (TH). This is a complex and unstable brain enzyme that catalyzes the rate-limiting step in the synthesis of dopamine and other catecholamine neurotransmitters. We have characterized these TH-loaded NPs to evaluate their potential for ERT in diseases associated with TH dysfunction. Our results show that TH can be loaded into the lipid core maltodextrin NPs with high efficiency, and both stability and activity are maintained through loading and are preserved during storage. Binding to NPs also favored the uptake of TH to neuronal cells, both in cell culture and in the brain. The internalized NP-bound TH was active as we measured an increase in intracellular L-Dopa synthesis following NP uptake. Our approach seems promising for the use of catalytically active NPs in ERT to treat neurodegenerative and neuropsychiatric disorders characterized by dopamine deficiency, notably Parkinson's disease.Lire moins >
Lire la suite >Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but ERT has been less successful for the correction of disorders with neurological manifestations. In this work, we have tested the functionality of nanoparticles (NP) composed of maltodextrin with a lipid core to bind and stabilize tyrosine hydroxylase (TH). This is a complex and unstable brain enzyme that catalyzes the rate-limiting step in the synthesis of dopamine and other catecholamine neurotransmitters. We have characterized these TH-loaded NPs to evaluate their potential for ERT in diseases associated with TH dysfunction. Our results show that TH can be loaded into the lipid core maltodextrin NPs with high efficiency, and both stability and activity are maintained through loading and are preserved during storage. Binding to NPs also favored the uptake of TH to neuronal cells, both in cell culture and in the brain. The internalized NP-bound TH was active as we measured an increase in intracellular L-Dopa synthesis following NP uptake. Our approach seems promising for the use of catalytically active NPs in ERT to treat neurodegenerative and neuropsychiatric disorders characterized by dopamine deficiency, notably Parkinson's disease.Lire moins >
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Équipe(s) de recherche :
Therapeutic innovation targetting inflammation
Date de dépôt :
2019-05-17T13:08:37Z
2023-12-01T14:53:42Z
2023-12-01T14:53:42Z