Human membrane metallo-endopeptidase-like protein degrades both beta-amyloid 42 and beta-amyloid 40

The endopeptidase properties of β and γ splice forms of human MMEL were determined in HEK293T cells transduced with the human cDNAs for the two splice forms; this showed degradation of both Aβ42 and Aβ40 by hMMEL-β but not hMMEL-γ. hMMEL-β activity was found at the extracellular surface with no significant secreted activity. hMMEL-γ was not expressed at the extracellular surface. Finally, it was found that hMMEL cleaves Aβ near the α-secretase site (producing Aβ1-17≫Aβ1-16). These data establish hMMEL as a mediator of Aβ catabolism and raise the possibility of its involvement in the etiology of AD and as a target for intervention.