Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-β

Jiyeon Han, Jiwon Yoon, Jeongcheol Shin, Eunju Nam, Tongrui Qian, Yulong Li, Kiyoung Park, Seung Hee Lee, Mi Hee Lim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The progression of neurodegenerative disorders can lead to impaired neurotransmission; however, the role of pathogenic factors associated with these diseases and their impact on the structures and functions of neurotransmitters have not been clearly established. Here we report the discovery that conformational and functional changes of a native neuropeptide, somatostatin (SST), occur in the presence of copper ions, metal-free amyloid-β (Aβ) and metal-bound Aβ (metal–Aβ) found as pathological factors in the brains of patients with Alzheimer’s disease. These pathological elements induce the self-assembly of SST and, consequently, prevent it from binding to the receptor. In the reverse direction, SST notably modifies the aggregation profiles of Aβ species in the presence of metal ions, attenuating their cytotoxicity and interactions with cell membranes. Our work demonstrates a loss of normal function of SST as a neurotransmitter and a gain of its modulative function against metal–Aβ under pathological conditions. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)1021-1030
Number of pages10
JournalNature Chemistry
Volume14
Issue number9
DOIs
StatePublished - Sep 2022

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