Kragten E, Lalande I, Zimmermann K, Roggo S, Schindler P, Muller D, van Oostrum J, Waldmeier P, Furst P
Novartis Pharma Research, Core Technology Area, CH-4002 Basel, Switzerland.
J Biol Chem. 1998 Mar 6;273(10):5821-8. doi: 10.1074/jbc.273.10.5821.
R-(-)-Deprenyl (Selegiline) represents one of the drugs currently used for the treatment of Parkinson's disease. This compound was shown to protect neurons or glias from programmed cell death in a variety of models. The mechanism of action of neuroprotection as well as inhibition of apoptosis remains elusive. CGP 3466 is a structurally related analog of R-(-)-deprenyl that exhibits virtually no monoamine oxidase type B inhibiting activity but is neuroprotective in the picomolar concentration range. We showed specific binding of CGP 3466 to glyceraldehyde-3-phosphate dehydrogenase by affinity binding, by affinity labeling, and by means of BIAcore(R) technology. Apoptosis assays based on the human neuroblastoma cell line PAJU established the importance of this interaction for mediating drug-induced inhibition of programmed cell death.
R-(-)-司来吉兰（Selegiline）是目前用于治疗帕金森病的药物之一。在多种模型中，该化合物已被证明可保护神经元或神经胶质细胞免于程序性细胞死亡。神经保护以及抑制细胞凋亡的作用机制仍不清楚。CGP 3466是R-(-)-司来吉兰的结构相关类似物，几乎不具有单胺氧化酶B型抑制活性，但在皮摩尔浓度范围内具有神经保护作用。我们通过亲和结合、亲和标记以及BIAcore(R)技术证明了CGP 3466与甘油醛-3-磷酸脱氢酶的特异性结合。基于人神经母细胞瘤细胞系PAJU的细胞凋亡分析确定了这种相互作用对于介导药物诱导的程序性细胞死亡抑制的重要性。
