Amyloid beta cleavage by ANA-TA9, a synthetic peptide from the ANA/BTG3 Box A region

Abstract

Introduction: We recently discovered a short synthetic peptide derived from the ANA/BTG3 protein Box A region called ANA-TA9 (SKGQAYRMI), which possesses catalytic activity. Herein we demonstrated the proteolytic activity of ANA-TA9 against amyloid beta 42 (Aβ42). Methods: The proteolytic activity of ANA-TA9 against both the authentic soluble form Aβ42 (a-Aβ42) and the solid insoluble form Aβ42 (s-Aβ42) was analyzed by high-performance liquid chromatography and mass spectrometry. Plasma clearance, brain uptake, and cell viability were examined. Results: ANA-TA9 cleaved not only a-Aβ42 but also s-Aβ42. Proteolytic activity was partially inhibited by 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, a serine protease inhibitor. Plasma clearance was very rapid, and the brain concentration indicated efficient brain delivery of ANA-TA9 via nasal application. Cell viability analysis indicated that ANA-TA9 did not display toxicity. Discussion: ANA-TA9 is an attractive potential candidate for the development of novel peptide drugs in Alzheimer's disease treatment.