p(HGNC:ADAM9)
Several zinc metallo proteinases such asTACE/ADAM17, ADAM9, ADAM10 and MDC-9 and the aspartyl protease BACE2 can cleave APP at the α-secretase site, located within the Aβ domain between Lys 16 and Leu 17 , essentially precluding the generation of intact Aβ(1). PubMed:18650430
As APP was found to be constitutively cleaved at the alpha-site to yield sAPP-alpha (Esch et al. 1990), three members of the a disintegrin and metalloproteinase (ADAMs), ADAM-10,ADAM-17 and ADAM-9 have been proposed as the alpha-secretase (Buxbaum et al. 1998; Koike et al. 1999;Lammich et al. 1999) PubMed:22122372
However, although sAPP-alpha generation is not affected in ADAM9/17 knock-down cell lines nor in mice carrying deficient ADAM9/17 genes (Weskamp et al. 2002; Kuhn et al. 2010), over-expression of ADAM9/17 does increase the level of sAPP-alpha under some conditions, suggesting that ADAM9 and ADAM17 are more likely involved in the regulated alpha-cleavage of APP rather than in constitutive alpha-cleavage PubMed:22122372
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