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Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease.
- Source :
- Journal of Alzheimer's Disease; 2020, Vol. 76 Issue 4, p1339-1345, 7p
- Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>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.<bold>Objective: </bold>We aimed to shed light on the mode of action of masitinib in Alzheimer's disease.<bold>Methods/results: </bold>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.<bold>Conclusion: </bold>These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition. [ABSTRACT FROM AUTHOR]
- Subjects :
- ALZHEIMER'S disease
TRANSGENIC mice
MAST cells
ALZHEIMER'S patients
SYNAPTOPHYSIN
TREATMENT effectiveness
TRYPTASE
BIOLOGICAL models
RESEARCH
NERVOUS system
ANIMAL experimentation
RESEARCH methodology
COGNITION
PROTEIN precursors
MEDICAL cooperation
EVALUATION research
COMPARATIVE studies
MEMBRANE proteins
THIAZOLES
PEPTIDES
MICE
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 13872877
- Volume :
- 76
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Journal of Alzheimer's Disease
- Publication Type :
- Academic Journal
- Accession number :
- 145184034
- Full Text :
- https://doi.org/10.3233/JAD-200466