Na Chanju, Kim Mingeun, Kim Gunhee, Lin Yuxi, Lee Young-Ho, Bal Wojciech, Nam Eunju, Lim Mi Hee
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Biopharmaceutical Research Center, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 28119, Republic of Korea.
ACS Chem Neurosci. 2025 Feb 19;16(4):732-744. doi: 10.1021/acschemneuro.4c00831. Epub 2025 Jan 30.
The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored. Here, we report the distinct aggregation behavior of -terminally truncated Aβ, specifically Aβ, in the absence and presence of either Zn(II), Aβ seeds, or both, and compare it to that of full-length Aβ. Our findings reveal notable differences in the aggregation profiles of Aβ and Aβ, largely influenced by their different Zn(II)-binding properties. These results provide insights into the mechanisms underlying the distinct aggregation behavior of truncated and full-length Aβ in the presence of Zn(II), contributing to a deeper understanding of AD pathology.
淀粉样β蛋白（Aβ）聚集体和金属离子在老年斑中的沉积是阿尔茨海默病（AD）的一个标志。在Aβ肽中观察到的修饰中，在苯丙氨酸4处的N端截断产生Aβ在AD受影响的大脑中非常普遍，并显著改变Aβ的金属结合和聚集特性。尽管老年斑中锌（II）含量丰富，但其对Aβ聚集和毒性的影响仍未得到探索。在这里，我们报告了在不存在或存在锌（II）、Aβ种子或两者的情况下，N端截断的Aβ，特别是Aβ的独特聚集行为，并将其与全长Aβ的聚集行为进行比较。我们的研究结果揭示了Aβ和Aβ聚集特性的显著差异，这在很大程度上受到它们不同的锌（II）结合特性的影响。这些结果为锌（II）存在下截断和全长Aβ独特聚集行为的潜在机制提供了见解，有助于更深入地理解AD病理学。
