中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (8): 1658-1659.doi: 10.4103/1673-5374.389643

• 观点:退行性病与再生 • 上一篇    下一篇

阿尔茨海默病中的小分子诱饵

  

  • 出版日期:2024-08-15 发布日期:2024-01-03

Small molecular decoys in Alzheimer’s disease

Sho Oasa, Valentina L. Kouznetsova, Igor F. Tsigelny, Lars Terenius*   

  1. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden (Oasa S, Terenius L) 
    San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USA (Kouznetsova VL, Tsigelny IF) 
    Department of Neurosciences, University of California San Diego, La Jolla, CA, USA (Tsigelny IF) 
    Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden (Terenius L)
  • Online:2024-08-15 Published:2024-01-03
  • Contact: Lars Terenius, PhD, Professor Emeritus, Lars.Terenius@ki.se.
  • Supported by:
    This work is being supported by several grant agencies as stated in the full paper (to LT).

摘要: https://orcid.org/0000-0003-2880-9576 (Lars Terenius)

Abstract: Recent progress in the treatment of Alzheimer’s disease (AD) using antibodies against amyloid sustains amyloid generation as a key process in AD. Amyloid formation starts with two amyloid-beta (Aβ) molecules interacting (dimer formation) followed by an accelerating build-up of so-called protofibrils, which turn into fibrils, which accumulate in the characteristic plaques. To interfere with the process at the root we used molecular modeling to define the surfaces of interaction in dimer formation. In a series of small molecules, we identified candidates that changed the course of interactions and generated aggregates with other macrostructures and reduced toxicity. We have introduced the term “decoys” to identify these molecules.