Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke.
Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke.
复制标题
DOI：
10.1007/s10495-008-0304-8
复制
发表时间：
2009-04
期刊：
影响因子：
7.2
通讯作者：
Yuan, Junying
中科院分区：
文献类型：
--
作者：
Yuan, Junying
中风是导致死亡和严重衰弱的主要原因，开发有效的治疗方法一直是一项重大挑战。过去十五年的深入研究已经揭示了许多调节因子以及调节神经元细胞死亡的相关机制。现在已经清楚，即使是短暂的缺血性中风也可能引发复杂的细胞事件，从而导致神经元细胞凋亡和坏死。尽管为经过验证的靶标开发特定化学抑制剂的努力在体外酶测定中已取得成功，但其中一些抑制剂在人类治疗中的开发往往因其体内生物利用度而受到阻碍。在开发过程的早期，可以通过优先确定可以有效化学靶向的关键靶点来强调以与体内疾病靶点兼容的方式化学靶向细胞机制的能力。通过饱和化学遗传学对细胞途径进行彻底询问可能会提供一种新的策略来识别可以化学靶向的多个关键分子实体，以便选择适合治疗中风等预期人类疾病的靶标。
It has been a major challenge to develop effective therapeutics for stroke, a leading cause of death and serious debilitation. Intensive research in the past fifteen years have implicated many regulators and the related mechanisms by which neuronal cell death is regulated. It is now clear that even a brief ischemic stroke may trigger complex cellular events that lead to both apoptotic and necrotic neuronal cell death in a progressive manner. Although efforts at developing specific chemical inhibitors for validated targets have been successful for in vitro enzymatic assays, the development of some of such inhibitors into human therapy has been often hindered by their in vivo bioavailability profile. Considerations for the ability to chemically target a cellular mechanism in manner compatible with disease targets in vivo might be emphasized early in the development process by putting a priority on identifying key targets that can be effectively targeted chemically. Thorough interrogation of cellular pathways by saturation chemical genetics may provide a novel strategy to identify multiple key molecular entities that can be targeted chemically in order to select a target suitable for the treatment of intended human diseases such as stroke.
登录
查看更多内容
DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
DOI：
10.1097/00004647-199704000-00002
发表时间：
1997-04-01
影响因子：
6.3
作者：
Hara, H;Fink, K;Moskowitz, MA
通讯作者：
Moskowitz, MA
DOI：
10.1073/pnas.94.5.2007
发表时间：
1997-03-04
影响因子：
11.1
作者：
Hara, H;Friedlander, RM;Moskowitz, MA
通讯作者：
Moskowitz, MA
影响因子：
--
作者：
Becattini, B;Sareth, S;Pellecchia, M
通讯作者：
Pellecchia, M
影响因子：
14.8
作者：
Degterev, Alexei;Hitomi, Junichi;Yuan, Junying
通讯作者：
Yuan, Junying