淀粉样蛋白Aβ的插膜作用可以抑制其形成纤维

作为老年性痴呆(AD)患者脑中淀粉样斑块的核心蛋白，β-淀粉样蛋白(Aβ)是从淀粉样前体蛋白(APP)水解而来。该蛋白是多种长度多肽的混合物，其中Aβ40和Aβ42是主要组分。分别研究了膜中胆固醇含量及溶液pH对Aβ40和Aβ42形成纤维的影响。电镜观察发现，含有胆固醇的脂质体几乎可以完全抑制Aβ40的纤维形成，而低pH只能部分地抑制Aβ42的纤维形成。单层膜的实验证明这两种因素都有利于Aβ40和Aβ42的插膜。构象研究表明插膜会诱导Aβ40和Aβ42的二级结构发生不同的变化。结果说明，Aβ40和Aβ42的插膜作用能够在一定程度上抑制蛋白形成纤维，但两者具有不同的抑制机制。

MEMBRANE INSERTION OF Aβ WOULD INDUCE ITS FIBRIL FORMATION

a-Amyloid peptide (A a ), the core protein of amyloid plaques in Alzheimer's disease, is a mixture of multilength peptides which are all derived from the amyloid precursor protei n (APP), and A a 40 and A a 42 are the two major components of the mixture. The effects of me mbrane cholesterol and buffer pH on the fibril formation of A a 40 and A a 42 were investigated respectively in this paper. The observation of electronic microscopy showed that cholesterol-containing liposome could nearl y completely inhibit the fibril formation of A a 40, and low pH could partly inhibit the fibrils formation of A a 42. Monolayer approach showed that A a 40 and A a 42 both were inclined to insert into membrane under the two above conditions. Further conformational measurements showed that the membrane in sertion had different effects on the secondary structure of A a 40 and A a 42. Therefore, the results of this paper indicate that the mechanisms to inh ibit the fibril formation of the two proteins are different, while the membrane insertion of A a 40 or A a 42 can reduce the fibril formation to a certain extent.