14 / 2021-07-14 15:59:39
Recognition and Removal of Amyloid-β by A Heteromultivalent Macrocyclic Co-assembly: A Potential Strategy for the Treatment of Alzheimer’s Disease
Alzheimer’s disease,heteromultivalent recognition,amyloid plaques,cognition,NMDA receptor channels
摘要录用
王晖 / 南开大学
许心心 / 南开大学
张涛 / 南开大学
The imbalance of amyloid-β (Aβ) production and clearance causes aggregation of Aβ1-42 monomers to form fibrils and amyloid plaques, which is an indispensable process in the pathogenesis of Alzheimer’s disease (AD), and eventually leads to pathological changes and cognitive impairment. Consequently, Aβ1-42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aβ1-42, inhibit Aβ1-42 fibrillation, eliminate amyloid plaques, improve cognitive impairments, and alleviate AD-like pathology is challenging. Here we designed a co-assembly composed of cyclodextrin (CD) and calixarene (CA), and used it as an anti-Aβ therapy agent. The CD-CA co-assembly was based on our previously reported heteromultivalent recognition strategy and was able to successfully eliminate amyloid plaques and degrade Aβ1-42 monomers in 5xFAD mice. More importantly, the co-assembly improved the recognition and spatial cognition deficits through the Morris water maze (MWM) test and novel object recognition (NOR) test. Moreover, the co-assembly enhanced the field excitatory postsynaptic potential (fEPSP) slopes after theta burst stimulation (TBS) in 5xFAD mice, which correlates with the expression of Ν-methyl-D-aspartate (NMDA) receptor channels. In addition, the co-assembly ameliorated AD-like pathology including prevention of neuronal apoptosis and oxidant stress, and alteration of M1/M2 microglial polarization states. This supramolecular approach made full use of both molecular recognition and self-assembly of macrocyclic amphiphiles, and is a promising novel strategy for AD treatment.

 
重要日期
  • 会议日期

    08月06日

    2021

    08月09日

    2021

  • 08月09日 2021

    注册截止日期

主办单位
中国神经科学学会离子通道与受体分会
承办单位
河北工业大学
历届会议
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