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

Abstract

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.

Keywords

• administered nasally (i.n.)
• Alzheimer's disease
• ANA/BTG3
• Aβ fragment peptide
• Aβ42
• catalytide