Volume 135, Issue 7 e202210209

Forschungsartikel

Amyloid Against Amyloid: Dimeric Amyloid Fragment Ameliorates Cognitive Impairments by Direct Clearance of Oligomers and Plaques

Hee Yang Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

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Dr. Seungyeop Baek,

Dr. Seungyeop Baek

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

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Minhae Cha,

Minhae Cha

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

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Prof. Seung-Hoon Yang,

Prof. Seung-Hoon Yang

Department of Medical Biotechnology, Dongguk University Jung-gu, Seoul, 04620 South Korea

These authors contributed equally to this work.

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Illhwan Cho,

Illhwan Cho

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Heewon Shin,

Heewon Shin

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Sejin Lee,

Dr. Sejin Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Hye Yun Kim,

Dr. Hye Yun Kim

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Songmin Lee,

Songmin Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Jisu Shin,

Dr. Jisu Shin

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Donghee Lee,

Dr. Donghee Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Kyeonghwan Kim,

Kyeonghwan Kim

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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InWook Park,

InWook Park

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Soljee Yoon,

Soljee Yoon

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Department of Integrative Biotechnology and Translational Medicine, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Jiyoon Kim,

Dr. Jiyoon Kim

Brain Science Institute, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

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Seong Jeong Park,

Seong Jeong Park

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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Dr. Seong Muk Kim,

Dr. Seong Muk Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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Ko Eun Kim,

Ko Eun Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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Hye Ju Kim,

Hye Ju Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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Min-Seok Oh,

Min-Seok Oh

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

Department of Stem Cell Biology, Konkuk University Gwangjin-Gu, Seoul, 05029 South Korea

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Dr. Gwan-Ho Lee,

Dr. Gwan-Ho Lee

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

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Dr. Byung-Yong Yu,

Dr. Byung-Yong Yu

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

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Priyadharshini Kannan,

Priyadharshini Kannan

Department of Biochemical Engineering, Gangneung-Wonju National University, Gangneung, 25457 South Korea

Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangwon-do, 25451 South Korea

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Dr. Keunwan Park,

Dr. Keunwan Park

Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangwon-do, 25451 South Korea

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Prof. YoungSoo Kim,

Corresponding Author

Prof. YoungSoo Kim

[email protected]

orcid.org/0000-0001-5029-7082

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Department of Integrative Biotechnology and Translational Medicine, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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Hee Yang Lee,

Hee Yang Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

Search for more papers by this author

Dr. Seungyeop Baek,

Dr. Seungyeop Baek

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

Search for more papers by this author

Minhae Cha,

Minhae Cha

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

These authors contributed equally to this work.

Search for more papers by this author

Prof. Seung-Hoon Yang,

Prof. Seung-Hoon Yang

Department of Medical Biotechnology, Dongguk University Jung-gu, Seoul, 04620 South Korea

These authors contributed equally to this work.

Search for more papers by this author

Illhwan Cho,

Illhwan Cho

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Heewon Shin,

Heewon Shin

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Dr. Sejin Lee,

Dr. Sejin Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Hye Yun Kim,

Dr. Hye Yun Kim

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Songmin Lee,

Songmin Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Jisu Shin,

Dr. Jisu Shin

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

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Dr. Donghee Lee,

Dr. Donghee Lee

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Kyeonghwan Kim,

Kyeonghwan Kim

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

InWook Park,

InWook Park

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Soljee Yoon,

Soljee Yoon

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Department of Integrative Biotechnology and Translational Medicine, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Search for more papers by this author

Dr. Jiyoon Kim,

Dr. Jiyoon Kim

Brain Science Institute, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

Search for more papers by this author

Seong Jeong Park,

Seong Jeong Park

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

Search for more papers by this author

Dr. Seong Muk Kim,

Dr. Seong Muk Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

Search for more papers by this author

Ko Eun Kim,

Ko Eun Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

Search for more papers by this author

Hye Ju Kim,

Hye Ju Kim

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

Search for more papers by this author

Min-Seok Oh,

Min-Seok Oh

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

Department of Stem Cell Biology, Konkuk University Gwangjin-Gu, Seoul, 05029 South Korea

Search for more papers by this author

Dr. Gwan-Ho Lee,

Dr. Gwan-Ho Lee

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

Search for more papers by this author

Dr. Byung-Yong Yu,

Dr. Byung-Yong Yu

Advanced Analysis and data Center, Korea Institute of Science and Technology Seongbuk-gu, Seoul, 02792 South Korea

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Priyadharshini Kannan,

Priyadharshini Kannan

Department of Biochemical Engineering, Gangneung-Wonju National University, Gangneung, 25457 South Korea

Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangwon-do, 25451 South Korea

Search for more papers by this author

Dr. Keunwan Park,

Dr. Keunwan Park

Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangwon-do, 25451 South Korea

Search for more papers by this author

Prof. YoungSoo Kim,

Corresponding Author

Prof. YoungSoo Kim

[email protected]

orcid.org/0000-0001-5029-7082

Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Department of Integrative Biotechnology and Translational Medicine, Yonsei University Yeonsu-gu, Incheon, 21983 South Korea

Amyloid Solution Bundang-gu, Seongnam-si, Gyeonggi-do, 13486 South Korea

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First published: 31 October 2022

https://doi.org/10.1002/ange.202210209

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Abstract

Amyloid-β (Aβ) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aβ drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood–brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aβ peptidomimetics that exploit the self-assembling nature of Aβ and penetrate the BBB. Herein, we designed a dimeric peptide drug candidate based on the N-terminal fragment of Aβ, DAB, found to cross the BBB and solubilize Aβ oligomers and fibrils. Administration of DAB reduced amyloid burden in 5XFAD mice, and downregulated neuroinflammation and prevented memory impairment in the Y-maze test. Peptide mapping assays and molecular docking studies were utilized to elucidate DAB-Aβ interaction. To further understand the active regions of DAB, we assessed the dissociative activity of DAB with sequence modifications.

Conflict of interest

SP, SMK, KEK, HJK, and YK are employees to Amyloid Solution, receive equity or equity options, and contributed to the development of technology discussed in this this publication. SYB, HJK, and YK are inventors on a patent licensed by Yonsei University to Amyloid Solution.

Open Research

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

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Volume135, Issue7

February 6, 2023

e202210209

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Amyloid Against Amyloid: Dimeric Amyloid Fragment Ameliorates Cognitive Impairments by Direct Clearance of Oligomers and Plaques

Abstract

Conflict of interest

Open Research

Data Availability Statement

Supporting Information

References

References

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Amyloid Against Amyloid: Dimeric Amyloid Fragment Ameliorates Cognitive Impairments by Direct Clearance of Oligomers and Plaques

Abstract

Conflict of interest

Open Research

Data Availability Statement

Supporting Information

References

References

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