ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Academic Article uri icon

abstract

  • Sequential proteolytic processing of the Amyloid Precursor Protein (APP) by beta- and gamma-secretases generates the 4-kDa amyloid (A beta) peptide, a key component of the amyloid plaques seen in Alzheimer's disease (AD). We and others have recently reported the identification and characterisation of an aspartic proteinase, Asp2 (BACE), as beta-secretase. Here we describe the characterization of a second highly related aspartic proteinase, Asp1 as a second beta-secretase candidate. Asp1 is expressed in brain as detected at the mRNA level and at the protein level. Transient expression of Asp1 in APP-expressing cells results in an increase in the level of beta-secretase-derived soluble APP and the corresponding carboxy-terminal fragment. Paradoxically there is a decrease in the level of soluble A beta secreted from the cells. Asp1 colocalizes with APP in the Golgi/endoplasmic reticulum compartments of cultured cells. Asp1, when expressed as an Fc fusion protein (Asp1-Fc), has the N-terminal sequence ALEP..., indicating that it has lost the prodomain. Asp1-Fc exhibits beta-secretase activity by cleaving both wild-type and Swedish variant (KM/NL) APP peptides at the beta-secretase site.

published proceedings

  • Mol Cell Neurosci

altmetric score

  • 17.25

author list (cited authors)

  • Hussain, I., Powell, D. J., Howlett, D. R., Chapman, G. A., Gilmour, L., Murdock, P. R., ... Christie, G.

citation count

  • 135

complete list of authors

  • Hussain, I||Powell, DJ||Howlett, DR||Chapman, GA||Gilmour, L||Murdock, PR||Tew, DG||Meek, TD||Chapman, C||Schneider, K||Ratcliffe, SJ||Tattersall, D||Testa, TT||Southan, C||Ryan, DM||Simmons, DL||Walsh, FS||Dingwall, C||Christie, G

publication date

  • January 2000