Inhibitory effect of chloroquine derivatives on presenilin 1 and ubiquilin 1 expression in Alzheimer's disease.
Alzheimer's disease is the common cause of dementia characterized by the accumulation of amyloid-β produced by breakage of amyloid-β precursor protein (APP). The present study was designed to synthesize and investigate the effect of chloroquine derivatives on the expression of presenilin. Among the five chloroquine derivatives (D1, D2, D3, D4 and D5) synthesized, D5 with diisopropyl substitution was found to be most effect. The results from western blot analysis showed the inhibition of presenilin 1 protein expression on treatment with chloroquine derivative D5 in Daudi cells. The results were also confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). It was observed that chloroquine derivative D5 downregulates presenilin expression via the inhibition of ubiquilin 1 expression. Thus our study demonstrates that chloroquine derivative D5 treatment can have preventive against Alzheimer's disease.
Department of Neurology, Xinxiang Central Hospital Xinxiang 453000, China.
Fang-Fang
FF
Zhang
Department of Neurology, Xinxiang Central Hospital Xinxiang 453000, China.
Jing
J
Li
D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C107792:UBQLN1 protein, human; D002738:Chloroquine
Chloroquine; diisopropyl substitution; inhibition; presenilin; ubiquilin 1