结合Hg (I) 和Hg (II) 离子与粉样β (Aβ) 变体影响它们的结构和聚合
Elina Berntsson1, Andra Noormägi2, Kärt Padari3
1Stockholms Universitet, Chemistry Section, SWEDEN.
Chembiochem : a European journal of chemical biology
|April 30, 2025
概括
暴露于可能会增加阿尔茨海默病的风险. 这项研究表明,与粉样β结合,改变它们的聚合,并可能导致阿尔茨海默氏症的病理.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
背景情况:
- 暴露于 (Hg) 是阿尔茨海默病 (AD) 的疑似危险因素,但缺乏确的证据和潜在机制.
- 阿尔茨海默病的特点是由聚合的粉样蛋白-β (Aβ) 形成的粉样蛋白斑块.
研究的目的:
- 为了研究无机 (HgI) 和HgII) 与粉样ββ (Aβ) 之间的体外相互作用.
- 阐明对Aβ聚合的影响及其在阿尔茨海默氏症神经病理学中的潜在作用.
主要方法:
- 使用了传输电子显微镜 (TEM) 和生物物理光谱技术.
- 使用Aβ(1-40),Aβ(4-40) 变体和Aβ(1-40) ((H6A,H13A,H14A) 突变体来研究相互作用.
- 对Aβ聚合的影响在HgI和HgII之间进行了比较.
主要成果:
- Hg(II) 与Aβ(1-40) 结合,表面亲和度为28±8μM,涉及N端的His残留物.
- Hg(II) 结合会诱导SDS微粒内的Aβ单体的结构变化 (卷轴对卷轴相互作用).
- 均Hg (I) 或Hg (II) 抑制正常的Aβ纤维化,促进大无形聚合物的形成.
结论:
- 与Aβ的结合改变了它们的聚合途径,可能导致阿尔茨海默病的病理学.
- 这些发现表明,由引起的蛋白质错误折叠和聚合可能是导致神经退行性疾病的一般毒性机制.
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