Inhibiting Acetylcholinesterase to Activate Pleiotropic Prodrugs with Therapeutic Interest in Alzheimer's Disease.
5-HT4 receptors
Alzheimer’s disease
MTDL
acetylcholinesterase
prodrug
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
31 Jul 2019
31 Jul 2019
Historique:
received:
18
07
2019
revised:
27
07
2019
accepted:
30
07
2019
entrez:
3
8
2019
pubmed:
3
8
2019
medline:
4
1
2020
Statut:
epublish
Résumé
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which is still poorly understood. The drugs currently used against AD, mainly acetylcholinesterase inhibitors (AChEI), are considered clinically insufficient and are responsible for deleterious side effects. AChE is, however, currently receiving renewed interest through the discovery of a chaperone role played in the pathogenesis of AD. But AChE could also serve as an activating protein for pleiotropic prodrugs. Indeed, inhibiting central AChE with brain-penetrating designed carbamates which are able to covalently bind to the enzyme and to concomitantly liberate active metabolites in the brain could constitute a clinically more efficient approach which, additionally, is less likely to cause peripheral side effects. We aim in this article to pave the road of this new avenue with an in vitro and in vivo study of pleiotropic prodrugs targeting both the 5-HT
Identifiants
pubmed: 31370232
pii: molecules24152786
doi: 10.3390/molecules24152786
pmc: PMC6696315
pii:
doi:
Substances chimiques
Carbamates
0
Cholinesterase Inhibitors
0
Ligands
0
Prodrugs
0
Receptors, Serotonin, 5-HT4
158165-40-3
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondation Vaincre Alzheimer
ID : FR-15072
Organisme : Fondation Plan Alzheimer
ID : TRIAD 016
Organisme : Conseil Régional de Normandie
ID : RIN
Organisme : European Cost Action Mu Ta Lig
ID : CA15135
Organisme : FEDER
ID : CERMN
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