Janet Johnston (240.16) presented a detailed study of the effect of proteasome and prolendopeptidase (PEP) inhibitors on Aβ production by SH SY 5Y human neuroblastoma cells stably transfected with SPA4CT (C99). Both the proteasome and PEP have been reported to directly alter Aβ production. However, Johnston presented compelling evidence that PEP does not influence γ-secretase processing, whereas specific inhibitors of the chymotrypsin-like activity of the proteasome elevate secretion of both Aβ40 and 42. The mechanism by which this elevation is mediated is currently under investigation.-Dominic Walsh.
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