1Department of Biochemistry and Biophysics, Stockholm University, Sweden; 2Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
Department of Biochemistry and Biophysics, Stockholm University, Sweden.
Acta Biochim Pol. 2021 Apr 28;68(2):169-179. doi: 10.18388/abp.2020_5493.
Alzheimer's disease (AD) is an incurable disease and the main cause of age-related dementia worldwide, despite decades of research. Treatment of AD with lithium (Li) has showed promising results, but the underlying mechanism is unclear. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. The plaques contain also metal ions of e.g. Cu, Fe, and Zn, and such ions are known to interact with Aβ peptides and modulate their aggregation and toxicity. The interactions between Aβ peptides and Li+ ions have however not been well investigated. Here, we use a range of biophysical techniques to characterize in vitro interactions between Aβ peptides and Li+ ions. We show that Li+ ions display weak and non-specific interactions with Aβ peptides, and have minor effects on Aβ aggregation. These results indicate that possible beneficial effects of Li on AD pathology are not likely caused by direct interactions between Aβ peptides and Li+ ions.
阿尔茨海默病（AD）是一种无法治愈的疾病，也是全世界与年龄相关的痴呆症的主要病因，尽管已经进行了几十年的研究。用锂（Li）治疗 AD 已经显示出有希望的结果，但潜在的机制尚不清楚。AD 大脑的病理特征是淀粉样斑块的沉积，主要由淀粉样-β（Aβ）肽聚集形成淀粉样纤维组成。斑块还含有例如铜、铁和锌等金属离子，已知这些离子与 Aβ 肽相互作用并调节其聚集和毒性。然而，Aβ 肽与 Li+离子之间的相互作用尚未得到很好的研究。在这里，我们使用一系列生物物理技术来表征 Aβ 肽与 Li+离子之间的体外相互作用。我们表明，Li+离子与 Aβ 肽显示出弱的和非特异性相互作用，并且对 Aβ 聚集的影响较小。这些结果表明，Li 对 AD 病理学的可能有益影响不太可能是由 Aβ 肽与 Li+离子之间的直接相互作用引起的。
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