Members of the disintegrin-metalloproteinases (ADAMs) family and ADAM10 and ADAM17 (TACE) in particular, are thought to have α-secretase activity in vivo (Buxbaum et al., 1998; Asai et al., 2003). Perhaps α-secretase activity is best known for alpha site proteolysis of APP. This processing of APP prevents the production of Aβ and thus potential amyloid pathology, linking α-secretase activity to AD. Interestingly, ADAM10 KO mice die at E9.5 and exhibit multiple brain defects (Hartmann et al., 2002). These mice have a similar phenotype to EGF receptor (EGFR) KO mice or TGFα KO mice (Tropepe et al., 1997), suggesting an important role for ADAM10 in cleavage-dependent activation of these components of EGF signaling (Hinkle et al., 2004; Lee et al., 2003; Sunnarborg et al., 2002). Notch1 and EGF receptor ligands are substrates of ADAM10 (Hartmann et al., 2002; Cornell and Eisen, 2002). Both ADAM10 and 17 are implicated in development-regulated notch signaling by ectodomain shedding of Notch ligands Delta and Jagged (LaVoie and Selkoe, 2003). While localization and function of TACE and ADAM10 in the SVZ have been described (Katakowski et al.,
