tailieunhanh - Báo cáo khoa học: Isoquinoline-1,3,4-trione and its derivatives attenuate b-amyloid-induced apoptosis of neuronal cells

Caspase-3 is a programmed cell death protease involved in neuronal apop-tosis during physiological development and under pathological conditions. It is a promising therapeutic target for treatment of neurodegenerative dis-eases. We reported previously that isoquinoline-1,3,4-trione and its deriva-tives inhibit caspase-3. | ễFEBS Journal Isoquinoline-1 3 4-trione and its derivatives attenuate b-amyloid-induced apoptosis of neuronal cells Ya-Hui Zhang1 z Hua-Jie Zhang1 z Fang Wu1 Yi-Hua Chen1 Xue-Qin Ma2 Jun-Qin Du1 Zhong-Liang Zhou2 Jing-Ya Li1 Fa-Jun Nan1 and Jia Li1 1 NationalCenter for Drug Screening Shanghai Institute of Materia Medica Shanghai Institutes for BiologicalSciences Chinese Academy of Sciences Shanghai China 2 East China NormalUniversity Academy of Life Science Shanghai China Keywords attenuate apoptosis b-amyloid caspase-3 inhibitor irreversible neuronal cell Correspondence J. Li or . Nan 189 Guo Shou Jing Road Shanghai 201203 China Fax 86 21 50801552 Tel 86 21 50801313 E-mail jli@ or fjnan@ These authors contributed equally to this work. Received 14 April2006 revised 27 August 2006 accepted 30 August 2006 doi 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 pancaspase inhibitors. Furthermore we show that these inhibitors attenuated apoptosis induced by b-amyloid 25-35 in PC12 cells and primary neuronal cells. Caspases are involved in apoptosis and the inflammatory response. Of the 14 members of this protease family caspase-3 is the key effector of caspase-dependent apoptosis and is activated in nearly every model of apoptosis including those with different signaling pathways. Caspase-3-deficient mice die prematurely with a vast excess of cells in their central nervous systems apparently as a result of decreased apoptosis of neuronal cells although apoptosis in other organs seems to occur normally 1 2 . Recent .