Title : Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative - Zhu_2019_Eur.J.Med.Chem_168_330 |
Author(s) : Zhu Z , Yang T , Zhang L , Liu L , Yin E , Zhang C , Guo Z , Xu C , Wang X |
Ref : Eur Journal of Medicinal Chemistry , 168 :330 , 2019 |
Abstract :
Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid beta-peptide (Abeta) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Abeta aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Abeta-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Abeta toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Abeta toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs. |
PubMedSearch : Zhu_2019_Eur.J.Med.Chem_168_330 |
PubMedID: 30826509 |
Zhu Z, Yang T, Zhang L, Liu L, Yin E, Zhang C, Guo Z, Xu C, Wang X (2019)
Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative
Eur Journal of Medicinal Chemistry
168 :330
Zhu Z, Yang T, Zhang L, Liu L, Yin E, Zhang C, Guo Z, Xu C, Wang X (2019)
Eur Journal of Medicinal Chemistry
168 :330