Abstract
Background and purpose: Montelukast, an antagonist of the
cysteinyl leukotrienes receptor 1, has been proposed for repurposing for
the treatment of neurodegenerative disorders, including Alzheimer’s
disease. Clinical trials are ongoing but the mechanisms supporting this
repurposing are still poorly understood.
Experimental Approach: Taking advantage of proteomics datasets
deposited in public repositories, data from mouse brain and a neuronal
chicken model exposed to the drug were reinterpreted in view of the
repurposing proposal.
Key Results: Montelukast increases the levels of presenilin 1,
nicastrin, neprilysin, and insulin-degrading enzyme, all of which are
involved in the amyloid aggregation and clearance processes. Hexokinase
1, malate and isocitrate dehydrogenate enzymes, from central metabolism
pathways, are also affected.
Conclusions and Implications: The data suggest that montelukast
is a modulator of the amyloid clearance process, favouring the removal
of aggregates and counterbalancing the overall amyloidogenic process.
Montelukast also acts on energy supply pathways, compensating the
ageing-associated decrease of the basal cell metabolism. Taken together,
these actions of montelukast clearly support its repurposing as a
candidate for Alzheimer’s disease management.