Glucose-dependent insulinotropic polypeptide (GIP) alleviates ferroptosis in aging-induced brain damage through the Epac/Rap1 signaling pathway
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Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacidhormone, exerts multifaceted effects in physiology, mostnotably in metabolism, obesity, and inflammation. Its significanceextends to neuroprotection, promoting neuronal proliferation,maintaining physiological homeostasis, and inhibiting celldeath, all of which play a crucial role in the context of neurodegenerativediseases. Through intricate signaling pathwaysinvolving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis andregulates a defense system against ferroptosis, an essential processin aging. Our study, utilizing GIP-overexpressing miceand in vitro cell model, elucidates the pivotal role of GIP inpreserving neuronal integrity and combating age-related damage,primarily through the Epac/Rap1 pathway. These findings shedlight on the potential of GIP as a therapeutic target for the pathogenesisof ferroptosis in neurodegenerative diseases and aging.
Abstract
Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacidhormone, exerts multifaceted effects in physiology, mostnotably in metabolism, obesity, and inflammation. Its significanceextends to neuroprotection, promoting neuronal proliferation,maintaining physiological homeostasis, and inhibiting celldeath, all of which play a crucial role in the context of neurodegenerativediseases. Through intricate signaling pathwaysinvolving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis andregulates a defense system against ferroptosis, an essential processin aging. Our study, utilizing GIP-overexpressing miceand in vitro cell model, elucidates the pivotal role of GIP inpreserving neuronal integrity and combating age-related damage,primarily through the Epac/Rap1 pathway. These findings shedlight on the potential of GIP as a therapeutic target for the pathogenesisof ferroptosis in neurodegenerative diseases and aging.
참고문헌 (24)
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