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铜和淀粉样蛋白-β存在下的天然神经肽生长抑素的构象和功能变化
作者:小柯机器人 发布时间:2022/7/16 23:25:16

韩国科学技术院(KAIST)Lim, Mi Hee团队报道了铜和淀粉样蛋白-β存在下的天然神经肽生长抑素的构象和功能变化。相关研究成果于2022年7月11日发表在国际顶尖学术期刊《自然—化学》。

神经退行性疾病的发展可导致神经传递受损。然而,与这些疾病相关的致病因素的作用及其对神经递质结构和功能的影响尚未明确确定。

该文中,研究人员报告了一项发现,在铜离子、金属游离淀粉样β(aβ)和金属结合aβ(金属-aβ)的存在下,天然神经肽生长抑素(SST)的构象和功能发生变化,这些都是阿尔茨海默病患者大脑中发现的病理因素。这些病理因素诱导SST的自组装,从而阻止其与受体结合。在相反的方向上,SST显著地改变了Aβ物种在金属离子存在下的聚集轮廓,减弱了它们的细胞毒性和与细胞膜的相互作用。研究表明,在病理条件下,SST作为神经递质的正常功能丧失,其对金属-aβ的调节功能增强。

附:英文原文

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

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

Issue&Volume: 2022-07-11

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.

DOI: 10.1038/s41557-022-00984-3

Source: https://www.nature.com/articles/s41557-022-00984-3

期刊信息

Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:21.687
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex