Membrane perturbation by the neurotoxic Alzheimer amyloid fragment beta 25-35 requires aggregation and beta-sheet formation.
Membrane perturbation by the neurotoxic Alzheimer amyloid fragment beta 25-35 requires aggregation and beta-sheet formation.
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神经毒性阿尔茨海默淀粉样蛋白片段 β 25-35 对膜的干扰需要聚集和形成 β 片层。
DOI：
10.1080/15216549800204332
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Kirino,Y
中科院分区：
文献类型：
--
作者：
Hirakura,Y;Satoh,Y;Hirashima,N;Suzuki,T;Kagan,BL;Kirino,Y
β-淀粉样肽（βAP）是阿尔茨海默病患者大脑中发现的老年斑和脑血管淀粉样沉积物的主要蛋白质成分。据报道，βAP只有在形成β折叠结构和聚集体时才具有神经毒性。在本研究中，我们报告了βAP的神经毒性核心，βAP-25 - 35（β25 - 35），扰乱脂质体膜，诱导膜电流，并仅在缓冲液条件下表现出溶血活性，其中肽形成β折叠结构并自发聚集。相比之下，β25 - 35在其单体无规卷曲结构中不会显著干扰脂质膜，并且不表现出溶血活性。刚果红对细胞膜电流也有抑制作用。β25 - 35与细胞膜相互作用的能力与之前报道的神经毒性高度相关。这些结果表明，聚集的β25 - 35引起的膜扰动构成了肽神经毒性的分子基础。
The β‐amyloid peptide (βAP) is a major proteinaceous component of senile plaques and cerebrovascular amyloid deposits found in the brain of patients with Alzheimer's disease. βAP is reported to be neurotoxic only when it forms β‐sheet structure and aggregates. In the present study, we report that the neurotoxic core of βAP, βAP‐25‐35 (β25‐35), perturbs liposome membranes, induces membrane current, and exhibits hemolytic activity only in a buffer condition where the peptide forms β‐sheet structure and spontaneously aggregates. In contrast, β25‐35 in its monomeric random coil structure does not perturb lipid membranes significantly, and exhibits no hemolytic activity. Also, the membrane current was inhibited by Congo Red. The ability of β25‐35 to interact with membranes highly correlates with its neurotoxicity reported previously. These results suggest that membrane perturbation by aggregated β25‐35 constitutes the molecular basis of the peptide's neurotoxicity.