Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease.
Alzheimer Disease
/ drug therapy
Amyloid beta-Peptides
/ pharmacology
Amyloid beta-Protein Precursor
/ genetics
Animals
Benzamides
Cognition
/ drug effects
Disease Models, Animal
Male
Mice, Transgenic
Piperidines
Presenilin-1
/ genetics
Pyridines
Synapses
/ drug effects
Thiazoles
/ administration & dosage
Alzheimer’s disease
cognition
drug evaluation
masitinib
mast
cells
preclinical
synapses
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
6
7
2020
medline:
4
6
2021
entrez:
6
7
2020
Statut:
ppublish
Résumé
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer's disease. We aimed to shed light on the mode of action of masitinib in Alzheimer's disease. We demonstrated here that chronic oral treatment of APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments. These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition.
Sections du résumé
BACKGROUND
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer's disease.
OBJECTIVE
We aimed to shed light on the mode of action of masitinib in Alzheimer's disease.
METHODS/RESULTS
We demonstrated here that chronic oral treatment of APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments.
CONCLUSION
These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition.
Identifiants
pubmed: 32623401
pii: JAD200466
doi: 10.3233/JAD-200466
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Benzamides
0
Piperidines
0
Presenilin-1
0
Pyridines
0
Thiazoles
0
masitinib
M59NC4E26P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM