Given that Down syndrome individuals have reduced PAI-1 in blood compared with controls [36], the aim of the present study is: a) to test the hypothesis that the calcineurin/NFAT pathway is involved in the NGF-induced upregulation of PAI-1 in neuronal cells and b) to analyse whether the overexpression of the Down syndrome-related proteins DYRK1A and RCAN1 can regulate the NGF effect on PAI-1 by modulating NFAT deactivation. The gene discussed is DYRK1A; the disease is Down syndrome.