Issue 43, 2019

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
20 Jun 2019
Accepted
16 Sep 2019
First published
19 Sep 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2019,10, 10149-10158

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, 10, 10149 DOI: 10.1039/C9SC03042E

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