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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.

SUBMITTER: Hatakawa Y 

PROVIDER: S-EPMC8012241 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Hatakawa Yusuke Y   Nakamura Rina R   Konishi Motomi M   Sakane Toshiyasu T   Tanaka Akiko A   Matsuda Akira A   Saito Motoaki M   Akizawa Toshifumi T  

Alzheimer's & dementia (New York, N. Y.) 20210331 1


<h4>Introduction</h4>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).<h4>Methods</h4>The proteolytic activity of ANA-TA9 against both the authentic soluble form Aβ42 (<i>a</i>-Aβ42) and the solid insoluble form Aβ42 (<i>s</i>-Aβ42) was analyzed by high-performance liquid chromatography and mass sp  ...[more]

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