FOXO3 and neurodegenerative disease: The adverse effects of SERPIN E1 on neurodegenerative diseases may also stem from its influence on one of the most relevant aging-related pathways encompassing the Insulin-like growth factor 1 (IGF1) - α-Klotho - SERPIN E1 - sirtuin 1 (SIRT1) - Forkhead box O3 (FOXO3a) - Peroxisome Proliferator-Activated Receptor γ (PPARγ) axis (Fig. 2).