Sato Naoyuki, Okochi Masayasu, Taniyama Yoshiaki, Kurinami Hitomi, Shimamura Munehisa, Takeuchi Daisuke, Hamada Hizuki, Fukumori Akio, Kiyosue Kazuyuki, Taguchi Takahisa, Tanaka Toshiyuki, Miyasaka Masayuki, Takeda Masatoshi, Ogihara Toshio, Morishita Ryuichi
Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Neurobiol Dis. 2006 Jun;22(3):487-95. doi: 10.1016/j.nbd.2005.12.010. Epub 2006 Feb 20.
Abeta is one of the primary therapeutic targets for Alzheimer disease (AD). Abeta vaccination induces the disappearance of Abeta deposits. Since few reports have focused on the reverse phase of Abeta aggregation, we established a new screening system, the in vitro Abeta sink assay, to clarify the process of dissociation of soluble forms from fibrils. Abeta42 was more resistant to dissociation from fibrils to monomers and/or low molecular weight (LMW) soluble oligomers than Abeta40. We applied this system to find a potential therapy for AD. Ultrasound irradiation significantly enhanced the dissociation of soluble Abeta from fibrils, while ultrasound experiments also confirmed the difference between Abeta40 and Abeta42. We found that some compounds enhanced the dissociation of Abeta from fibrils. Here, we proposed that Abeta42 was more resistant to dissociation from fibrils to monomers and/or LMW soluble oligomers than Abeta40, and this system might be useful to identify dissociation of soluble Abeta from fibrils.
淀粉样β蛋白（Aβ）是阿尔茨海默病（AD）的主要治疗靶点之一。Aβ疫苗接种可导致Aβ沉积物消失。由于很少有报告关注Aβ聚集的逆转阶段，我们建立了一种新的筛选系统——体外Aβ汇分析，以阐明可溶形式从纤维中解离的过程。与Aβ40相比，Aβ42从纤维解离为单体和/或低分子量（LMW）可溶性寡聚体的能力更弱。我们应用该系统寻找AD的潜在治疗方法。超声照射显著增强了可溶性Aβ从纤维中的解离，同时超声实验也证实了Aβ40和Aβ42之间的差异。我们发现一些化合物可增强Aβ从纤维中的解离。在此，我们提出，与Aβ40相比，Aβ42从纤维解离为单体和/或LMW可溶性寡聚体的能力更弱，并且该系统可能有助于识别可溶性Aβ从纤维中的解离。
