Ferrero Alejandro, Cereseto Marina
UBA, Junín 956, 5to piso, 1113 Ciudad autónoma de Buenos Aires.
Vertex. 2004;15(58):251-8.
Excitotoxic cell death is a direct consequence of the glutamate interaction with its receptors, through which the neuronal excitatory impulses are transmitted. Despite some well characterized aspects of this process--such as a subsequent increase in intracellular calcium concentrations and the activation of some enzymatic mechanisms--the specific intracellular pathways which mediate this cell death mechanism are still unknown. In this article, we summarize the different theories which try to explain how the neurotoxic effect development goes on beyond the glutamate receptor interaction. Apart from that, since there is a lot of evidence for the role of excitotoxicity in the aetiology and the progression of many human neurodegenerative diseases, we mention some of the experimental evidence relating certain pathologies to this form of cell death. Finally, and due the increasing necessity of more effective treatments for such diseases, we describe some anti-excitotoxic agents and its mechanisms of action.
兴奋性毒性细胞死亡是谷氨酸与其受体相互作用的直接后果,神经元兴奋性冲动通过该受体进行传递。尽管这一过程的一些方面已得到充分表征,例如细胞内钙浓度随后升高以及某些酶促机制的激活,但介导这种细胞死亡机制的具体细胞内途径仍然未知。在本文中,我们总结了不同的理论,这些理论试图解释神经毒性作用如何在谷氨酸受体相互作用之外继续发展。除此之外,由于有大量证据表明兴奋性毒性在许多人类神经退行性疾病的病因学和进展中起作用,我们提及了一些将某些病理与这种细胞死亡形式相关联的实验证据。最后,由于对这类疾病的更有效治疗的需求日益增加,我们描述了一些抗兴奋性毒性药物及其作用机制。