Thimet Oligopeptidase 1 (THOP1)

Proteases involved in the amyloidogenic processing of amyloid precursor protein (APP) represent likely candidates for the site of mutation in a form of familial Alzheimer disease (AD2). Formation of toxic amyloid in the brain parenchyma and cerebral vasculature in Alzheimer disease requires the proteolytic release of the 39- to 43-amino acid amyloid beta peptide from its precursor, APP. Sequence comparison revealed that this enzyme, THOP1, has high homology to the previously described rat metalloendopeptidase 24.15 (EC 3.4.24.15). The beta-secretase-like activity of the human enzyme in vitro in combination with its localization in neurons and its co-localization with APP in transport vesicles purified from rabbit optic nerve rendered this enzyme an interesting candidate for amyloidogenic processing of APP.