α-secretase-like metalloprotease-dependent ectodomain shedding is an event common to numerous neurogenic signals, including insulin-like growth factor-1 (IGF-1) (McElroy et al., 2007), Notch1 (Brou et al., 2000), E-cadherin (Maretzky et al., 2005a), L1 (Maretzky et al., 2005b), ErbB4 (Rio et al., 2000), and EGFR ligands (Sahin et al., 2004). Both ADAM10 and 17 play major roles in the ectodomain shedding of EGFR ligands (Sahin et al., 2004). Soluble APPα (sAPPα), a cleavage product of α-secretase regulates proliferation of EGF-responsive NSC in the SVZ (Caille et al., 2004). Thus, FAD-linked reduction in sAPP levels may affect extent of neural progenitor cell proliferation and the amount of the NSC pool. Likewise, alterations in α-secretase activity may affect neurogenesis.
