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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Glucose-dependent insulinotropic polypeptide (GIP) alleviates ferroptosis in aging-induced brain damage through the Epac/Rap1 signaling pathway

  • Jiwon Ko (Institute of Life Science and Biotechnology, Kyungpook National University) ;
  • Soyoung Jang (School of Life Science and Biotechnology, College of Natural Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University) ;
  • Soyeon Jang (Institute of Life Science and Biotechnology, Kyungpook National University) ;
  • Song Park (Division of Animal Science, Gyeongsang National University) ;
  • Junkoo Yi (School of Animal Life Convergence Science, Hankyong National University) ;
  • Dong Kyu Choi (School of Life Science and Biotechnology, College of Natural Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University) ;
  • Seonggon Kim (Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Myoung Ok Kim (Department of Animal Science and Biotechnology, Kyungpook National University) ;
  • Su-Geun Lim (Institute of Life Science and Biotechnology, Kyungpook National University) ;
  • Zae Young Ryoo (School of Life Science and Biotechnology, College of Natural Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University)
  • Received : 2024.05.07
  • Accepted : 2024.07.24
  • Published : 2024.09.30
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Abstract

Glucose-dependent insulinotropic polypeptide (GIP), a 42-amino-acid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging.

Keywords

Acknowledgement

This research was supported by Global - Learning & Academic research institution for Master's·PhD students, and Postdocs (LAMP) Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. RS-2023-00301914).

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