Zhang Yang-Xin, Wang Shao-Wei, Lu Shuai, Zhang Ling-Xiao, Liu Dong-Qun, Ji Mei, Wang Wei-Yun, Liu Rui-Tian
School of Life Science, Anhui Agricultural University, Hefei, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
FEBS Lett. 2017 Nov;591(21):3615-3624. doi: 10.1002/1873-3468.12871. Epub 2017 Oct 13.
Beta-amyloid (Aβ) oligomers are strongly associated with the cascade of harmful events leading to neurodegeneration in Alzheimer's disease (AD). Elimination of Aβ oligomers or inhibition of Aβ assembly is a valuable therapeutic approach for the treatment of AD. Here, we obtained a mimotope of Aβ oligomers, AOEP2, by screening a peptide library using oligomer-specific antibodies. The antibodies induced by AOEP2 specifically recognize Aβ oligomers rather than monomers and fibrils. Interestingly, the AOEP2 peptide binds to Aβ monomers and inhibits the formation of Aβ oligomers and β-sheet structure, reduces Aβ42-induced neurotoxicity, and decreases the release of proinflammatory cytokines. Taken together, AOEP2, a novel multifunctional peptide directly or indirectly targeting Aβ, has promising therapeutic potential for AD.
β-淀粉样蛋白（Aβ）寡聚体与导致阿尔茨海默病（AD）神经退行性变的一系列有害事件密切相关。消除Aβ寡聚体或抑制Aβ组装是治疗AD的一种有价值的治疗方法。在此，我们通过使用寡聚体特异性抗体筛选肽库获得了Aβ寡聚体的模拟表位AOEP2。AOEP2诱导产生的抗体特异性识别Aβ寡聚体而非单体和纤维。有趣的是，AOEP2肽与Aβ单体结合，抑制Aβ寡聚体和β-折叠结构的形成，降低Aβ42诱导的神经毒性，并减少促炎细胞因子的释放。综上所述，AOEP2是一种直接或间接靶向Aβ的新型多功能肽，对AD具有有前景的治疗潜力。
