Jump to main content
Jump to site search


Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation

Author affiliations

Abstract

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative illnesses in the elderly. Accumulation of amyloid-β peptide (Aβ) and inflammation play critical roles in the pathogenesis and development of AD. Multi-target drugs may interdict the progress of AD through a synergistic mechanism. A neuromodulator, 2-((1H-benzo[d]imidazole-2-yl)methoxy)benzoic acid (BIBA), consisting of an Aβ-targeting group and a derivative of anti-inflammatory aspirin was designed as a potential anti-AD agent. BIBA exhibits a remarkable inhibitory effect on the self- and metal-induced Aβ aggregations and shows outstanding anti-inflammatory activity simultaneously. The neurotoxicity of Aβ aggregates is attenuated, and the production of pro-inflammatory cytokines (PICs), such as IL-6, IL-1β and TNF-α, in microglia stimulated by lipopolysaccharide (LPS) or Aβ is reduced. Owing to the synergy between the inhibition of Aβ oligomerization and downregulation of PICs, BIBA markedly prolongs the lifespan and relieves the Aβ-induced paralysis of Aβ-transgenic Caenorhabditis elegans, thus showing the potential to ameliorate the symptoms of AD through inhibiting Aβ neurotoxicity and deactivating microglia. These findings demonstrate that both Aβ aggregation and neuroinflammation are therapeutic targets for anti-AD drugs, and dual-functional agents that integrate anti-Aβ and anti-inflammatory capabilities have great advantages over the traditional single-target agents for AD treatment.

Graphical abstract: Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation

Back to tab navigation

Supplementary files

Publication details

The article was received on 20 Jun 2019, accepted on 16 Sep 2019 and first published on 19 Sep 2019


Article type: Edge Article
DOI: 10.1039/C9SC03042E
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

  •   Request permissions

    Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation

    T. Yang, Z. Zhu, E. Yin, Y. Wang, C. Zhang, H. Yuan, H. Zhang, S. Jin, Z. Guo and X. Wang, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC03042E

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements