Development of RNA aptamer against toxic Aβ oligomer

淀粉样蛋白β蛋白(Aβ)是阿尔茨海默病的病原体，聚集并表现出神经毒性。已有文献表明，β寡聚体(毒性二聚体)主要与神经毒性有关。我们已经证明了22位和23位转角结构的形成在Aβ齐聚过程中起着关键作用。然而，由于Aβ具有很强的聚集能力，因此合成Aβ低聚体是相当困难的。为了研制抗A-β毒性二聚体的核酸脱氧核糖核酸异构体，我们合成了A-β-40二聚体，其中ALA30被二胺基戊二酸取代为分子间连接物。针对Aβ40二聚体的适配子的开发正在进行中。

Amyloid β-protein (Aβ), a causative agent of Alzheimer’s disease, aggregates and shows neurotoxicity. It has been well documented that Aβ oligomer (toxic dimer) is mostly related to the neurotoxicity. We have demonstrated that the formation of turn structure at position 22 and 23 plays a critical role in the oligomerization of Aβ. However, it is quite difficult to synthesize Aβoligomer due to the potent ability of Aβ to aggregate. To develop RNA apatamer against toxic Aβdimer, we synthesized Aβ40 dimer, in which Ala30 was substituted with diaminopimelic used as anintermolecular linker. The development of aptamer against Aβ40 dimer is under way.