IDENTIFICATION OF A NOVEL SERINE PROTEASE-LIKE MOLECULE IN HUMAN BRAIN

Proteolysis of the amyloid beta protein precursor (APP) is a key event in the development of Alzheimer's disease. In our search for protease s that can cleave APP and liberate the amino terminus of the amyloidog enic beta protein, we characterized a calcium-dependent serine proteas e (CASP) which is present in reactive astrocytes and cross-reacts with anti-cathepsin G antibodies. We wanted to take advantage of this cros s-reactivity to clone the cDNA of GASP and eventually evaluate its tis sue distribution. Screening of two human fetal brain cDNA libraries wi th anti-cathepsin G antibodies led to the identification of a cDNA cod ing for a novel protein whose only homology to known proteins is to th e active site of trypsin-type serine proteases. We called this protein the novel serine protease (NSP). NSP exists in at least three differe ntially spliced forms, one of which is expressed predominantly in brai n and testis. Immunohistochemistry and immunoprecipitation with antibo dies generated against NSP show that it is expressed and secreted by a variety of cells and that, in brain, it is found primarily in cerebro vascular smooth muscle cells and reactive astrocytes. (C) 1998 Elsevie r Science B.V.