新型聚集抑制剂对β-淀粉样蛋白介导的长时程增强抑制的反转

Inhibition of LTP by β-amyloid Prevented by Novel Aggregation Inhibitors

研究探讨了2种Aβ聚集抑制剂在Aβ对LTP的抑制效能上的作用.在海马齿状回上,高频刺激前持续灌流Aβ(500nmol.L-1)40min后,高频刺激诱导的LTP完全被抑制,这种抑制能被M1(5μmol.L-1)和M2(10μmol.L-1)所反转.中国仓鼠卵细胞自然分泌的人体Aβ在极低的浓度下(1.1 nmol.L-1)也完全抑制了LTP的诱导,此Aβ仅含单体和寡聚体,不含有纤维型和原纤维型.研究表明:寡聚型Aβ形成的阻断可以逆转Aβ对LTP诱导的抑制.这些发现提示阻断寡聚体Aβ形成的药物可以用来治疗AD.

In this study, the role of two aggregation inhibitors in the inhibition of Aβ on LTP is investigated. The induction of LTP by a brief HFS in the dentate gyrus is prevented by pre-perfusion of Aβ （500μmol·L^-1） for 40min prior to HFS. This inhibition can be prevented by M1 （5μmol·L^-1）, and M2 （10 μmol·L^-1）. Naturally secreted Chinese hamster ovary cell-derived human Aβ, which contains only Aβ monomer and oligomers and is free of fibrils and protofibrils, also completely inhibits induction of LTP in a low concentration（1.1 μmol·L^-1）： The studies show that the blockade of oligomer Aβ formation prevents the Aβ inhibition of LTP. These findings indicate that therapeutic treatment for AD may include agents that block oligomer Aβ formation.