Isoquinoline-1,3,4-trione and its derivatives attenuate beta-amyloid-induced apoptosis of neuronal cells.
Caspase-3 is a programmed cell death protease involved in neuronal apoptosis during physiological development and under pathological conditions. It is a promising therapeutic target for treatment of neurodegenerative diseases. We reported previously that isoquinoline-1,3,4-trione and its derivatives inhibit caspase-3. In this report, we validate isoquinoline-1,3,4-trione and its derivatives as potent, selective, irreversible, slow-binding and pan-caspase inhibitors. Furthermore, we show that these inhibitors attenuated apoptosis induced by beta-amyloid(25-35) in PC12 cells and primary neuronal cells.
Zhang
Ya-Hui
YH
National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhang
Hua-Jie
HJ
Wu
Fang
F
Chen
Yi-Hua
YH
Ma
Xue-Qin
XQ
Du
Jun-Qin
JQ
Zhou
Zhong-Liang
ZL
Li
Jing-Ya
JY
Nan
Fa-Jun
FJ
Li
Jia
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D061945:Caspase Inhibitors; D007546:Isoquinolines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C515844:isoquinoline-1,3,4-trione