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The protection of novel 2-arylethenylquinoline derivatives against impairment of associative learning memory induced by neural Aβ in C. elegans Alzheimer’s disease model

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Abstract

Cerebral deposition of amyloid β-peptide (Aβ), a fundamental feature of Alzheimer’s disease (AD), damages the neurocytes and impairs the cognition functions and associative learning memory of AD patients. A series of novel 2-arylethenylquinoline derivatives were synthesized and evaluated in our previous study, which inhibited Aβ aggregation in vitro effectively at the concentration of 20 μmol/L and exhibited high antioxidant activity. In order to verify the capacity of anti-AD in vivo, the transgenic Caenorhabditis elegans (C. elegans) strain CL2355 expressing neural Aβ was employed as the AD model to investigate the neuroprotective activity of seven high-potential compounds (4a1, 4a2, 4b1, 4b2, 4c1, 4c2, 4c3) selected from those derivatives. Learning memory associated chemotaxis assay was performed to evaluate the neural repairment capacity. The underlying mechanism was investigated by mRNA analysis of gene and heat shock protein genes (hsp-16.1 and hsp-16.2) and Western blot of Aβ. Our data indicated that among seven tested compound, 4b1 and 4c2 reduced Aβ-induced stress, suppressed the expression of neural Aβ monomers and toxic oligomers, and recovered the damaged associative learning memory in C. elegans AD model. These findings further confirmed their potentials to become valuable agents for AD therapy.

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Abbreviations

AD:

Alzheimer’s disease

ANOVA:

Analysis of variance

Aβ:

Amyloid beta-peptide

C. elegans :

Caenorhabditis elegans

CI:

Chemotactic index

DMSO:

Dimethyl sulfoxide

E. coli :

Escherichia coli

hsp-16.1 :

Heat shock protein 16.1 gene

hsp-16.2 :

Heat shock protein 16.2 gene

L1 stage:

Larvae one stage

NGM:

Nematode growth medium

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

SD:

Standard deviations

snb-1 :

Synaptobrevin ortholog

Trizol:

Total RNA Extractor

YA stage:

Young adulthood stage

*4a1, 4a2, 4b1, 4b2, 4c1, 4c2 and 4c3:

Seven tested 2-arylethenylquinoline derivatives

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Acknowledgements

The nematode strains used in this work were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH National Center for Research Resources. The authors gratefully acknowledge the financial supports from National Natural Science Foundation of China (Grant Nos. 21375152, 21675177 and 81273433) and Guangdong Provincial Science and Technology Projects (Grant No. 2016B030303002).

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Correspondence to Zuanguang Chen.

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He, Q., Huang, G., Chen, Y. et al. The protection of novel 2-arylethenylquinoline derivatives against impairment of associative learning memory induced by neural Aβ in C. elegans Alzheimer’s disease model. Neurochem Res 42, 3061–3072 (2017). https://doi.org/10.1007/s11064-017-2339-0

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