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.

Activation of Microbiota Sensing – Free Fatty Acid Receptor 2 Signaling Ameliorates Amyloid-β Induced Neurotoxicity by Modulating Proteolysis-Senescence Axis

“…Additionally, the CL2355 strain overexpresses human Aβ when grown at 22°C and develops paralysis, but grows normally at 16°C (Ahmad and Ebert, 2020 ). CL2355 is a good model for measuring AD-like chemotactic cognition/memory behaviors compared to the CL2122 strain, which shows normal chemotaxis (cognition/memory; He et al, 2017 ). Interestingly, Fenchol treatment significantly increased the lifespan in the CL2006 and CL4176 strains and reduced Aβ accumulation.…”

Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan ofCaenorhabditis elegansvia DAF-16 and HSF-1

“…C. elegans has impressive chemotaxis behavior. To analyze whether C. elegans use chemotaxis to avoid SDG, we performed chemotaxis assays (see Figure 1(d) ) using synchronized late L4 larvae or young adult wild-type N2 worms as described previously [ 18 , 19 ]. About 200 worms were placed in the center of an assay NGM plate (diameter: 3.5 cm), which contain 50, 200, or 500 μ M of SDG plus 2% tetramisole hydrochloride to paralyze the worms on one side of the plate (A side) and H 2 O as solvent control plus 2% tetramisole hydrochloride on the opposite side of the plate (B side).…”

The Antioxidant Capacity In Vitro and In Vivo of Polysaccharides From Bergenia emeiensis

“…Lublin et al found that caffeine, tannic acid and bacitracin could protect C. elegans CL2006 strain from Aβ induced toxicity [ 50 ]. He et al used C. elegans CL2355 as an Alzheimer disease model to test the neuroprotective activities of seven new 2-arylvinylquinoline derivatives [ 51 ]. C. elegan s is maintained at a low temperature.…”