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pubmed:abstractText |
During intramembrane proteolysis of ?-amyloid protein precursor (?APP) by presenilin (PS)/?-secretase, ?-cleavages at the membrane-cytoplasmic border precede ?-cleavages at the middle of the transmembrane domain. Generation ratios of A?42, a critical molecule for Alzheimer's disease (AD) pathogenesis, and the major A?40 species might be associated with ?48 and ?49 cleavages, respectively. Medicines to downregulate A?42 production have been investigated by many pharmaceutical companies. Therefore, the ?-cleavages, rather than the ?-cleavage, might be more effective upstream targets for decreasing the relative generation of A?42. Thus, one might evaluate compounds by analyzing the generation ratio of the ?APP intracellular domain (AICD) species (?-cleavage-derived), instead of that of A?42.
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