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

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 Aβ 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.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

He Q,Huang G,Chen Y,Wang X,Huang Z,Chen Z

doi

10.1007/s11064-017-2339-0

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

3061-3072

issue

11

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-017-2339-0

journal_volume

42

pub_type

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