In Alzheimer’s disease (AD) models, PAI-1 confers neuroprotection against NMDA receptor-mediated excitotoxicity via the TGF-β1/Smad3 signaling pathway, whereas astrocyte-derived PAI-1 enhances PC-12 cell survival through the TrkA receptor and c-Jun/AP-1 pathway activation [98]. This evidence concerns the gene SMAD3 and Alzheimer disease.