An aminopeptidase from Streptomyces sp. KK565 degrades beta amyloid monomers, oligomers and fibrils.

The accumulation of beta amyloid (Aβ) has been a primary target for Alzheimer disease therapeutic strategies. Previously, we discovered an activity from Streptomyces sp. KK565 growth media that inhibits Aβ aggregation. The active component was an aminopeptidase and named Streptomyces sp. KK565 aminopeptidase (SKAP). SKAP cleaved N-terminal amino-acids of Aβ(1-42) monomer, inhibited formation of fibrils and protected Aβ(1-42)-induced neurotoxicity. Over-expression of a human homolog of SKAP, glutamate carboxypeptidase II (hGCPII) in Aβ-oversynthesizing cells dramatically reduced the Aβ levels. These findings suggest a possible role of M28 family peptidases in preventing Aβ deposits in mammalian brain.