Cadet Jean Lud, Jayanthi Subramaniam, Deng Xiaolin
Molecular Neuropsychiatry Branch, NIH, NIDA, Intramural Research Program, Department of Health and Human Services, 5500 Nathan Shock Dr., Baltimore, Maryland 21224, USA.
FASEB J. 2003 Oct;17(13):1775-88. doi: 10.1096/fj.03-0073rev.
Methamphetamine (METH) is a drug of abuse that has long been known to damage monoaminergic systems in the mammalian brain. Recent reports have provided conclusive evidence that METH can cause neuropathological changes in the rodent brain via apoptotic mechanisms akin to those reported in various models of neuronal death. The purpose of this review is to provide an interim account for a role of oxygen-based radicals and the participation of transcription factors and the involvement of cell death genes in METH-induced neurodegeneration. We discuss data suggesting the participation of endoplasmic reticulum and mitochondria-mediated activation of caspase-dependent and -independent cascades in the manifestation of METH-induced apoptosis. Studies that use more comprehensive approaches to gene expression profiling should allow us to draw more instructive molecular portraits of the complex plastic and degenerative effects of this drug.
甲基苯丙胺（METH）是一种滥用药物，长期以来人们都知道它会损害哺乳动物大脑中的单胺能系统。最近的报告提供了确凿证据，表明METH可通过类似于各种神经元死亡模型中报道的凋亡机制，在啮齿动物大脑中引起神经病理变化。本综述的目的是对基于氧的自由基的作用、转录因子的参与以及细胞死亡基因在METH诱导的神经退行性变中的参与提供一个中期说明。我们讨论了一些数据，这些数据表明内质网和线粒体介导的半胱天冬酶依赖性和非依赖性级联反应的激活参与了METH诱导的细胞凋亡的表现。使用更全面的方法进行基因表达谱分析的研究，应能使我们描绘出这种药物复杂的可塑性和退行性作用更具启发性的分子图谱。
