Cells that co-express an amyloid precursor protein and an alpha-secretase, a test method for the identification of alpha-secretase-active substances and one for the identification of further secretases, a test method for determining the susceptibility to Alzheimer's disease and the use of nucleic acids which code for an alpha-secretase , for gene therapy

摘要

The invention relates to a recombinant cell which expresses a substrate protein comprising at least one sequence region of 18 amino acids of the human amyloid precursor protein (APP) or a homologous protein. The sequence region contains the alpha -secretase cleavage site as well as 6 amino acid rests at the amino terminal and 12 amino acid rests at the carboxy terminal, in relation to the alpha -secretase cleavage site, and contains either a) a recombinant nucleic acid comprising at least one gene for a protease protein which contains either the sequence region(s), required for proteolytic action, of the disintegrin metalloprotease ADAM 10 obtained from cattle (Bos taurus), humans or another mammal or represents a mutein of a mammalian disintegrin metalloprotease ADAM 10 which has essentially the same enzymatic properties, the gene or genes being controlled by a heterologous promotor; or b) heterologous RNA coding for a substrate protein and a protease protein. The invention also relates to the use of the above cells.