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.
NK cells are an important arm of the innate immune system, and they constitutively express the NKp30 receptor. NKp30-mediated responses are triggered by the binding of specific ligands, such as tumour cell-derived B7-H6, and involve the secretion of cytotoxic mediators TNF-α, IFN-γ, perforins and granzymes. The latter two constitute a target cell-directed response that is critical in the process of immunosurveillance. The structure of NKp30 is presented, focusing on the ligand-binding site, on the ligand-induced structural changes, and on the experimental data available correlating structure and binding affinity. The translation of NKp30 structural changes to disease progression is also reviewed. NKp30 role in immunotherapy has been explored in chimeric antigen receptor T-cell (CAR-T) therapy. However, antibodies or small ligands targeting NKp30 have not yet been developed. The data reviewed unveils the key structural aspects that must be considered for drug design in order to develop novel immunotherapy approaches.