Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 76, Issue 4, Pages 1339-1345Publisher
IOS PRESS
DOI: 10.3233/JAD-200466
Keywords
Alzheimer's disease; cognition; drug evaluation; masitinib; mast cells; preclinical; synapses
Categories
Funding
- BPI France
- INSERM
- CNRS
- Universite Sorbonne
- program Investissementsd'avenir [ANR-10-IAIHU-06 (IHU-A-ICM)]
Ask authors/readers for more resources
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-I3 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available