Ju Kevin L, Manley Nathan C, Sapolsky Robert M
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Exp Neurol. 2008 Apr;210(2):602-7. doi: 10.1016/j.expneurol.2007.12.008. Epub 2007 Dec 23.
A number of gene therapy approaches have been developed for protecting neurons from necrotic neurological insults. Such therapies are limited by the need for transcription and translation of the protective protein, delaying therapeutic impact. As an alternative, we explore the neuroprotective potential of protein therapy, using a fusion protein comprised of the death-suppressing BH4 domain of the Bcl-xL protein and the protein transduction domain of the human immunodeficiency virus Tat protein. This fusion protein decreased neurotoxicity caused by the excitotoxins glutamate and kainic acid in primary hippocampal cultures, and decreased hippocampal damage in vivo in an excitotoxic seizure model.
已经开发出多种基因治疗方法来保护神经元免受坏死性神经损伤。此类疗法受到保护蛋白转录和翻译需求的限制，延迟了治疗效果。作为一种替代方法，我们探索了蛋白质疗法的神经保护潜力，使用一种融合蛋白，该融合蛋白由Bcl-xL蛋白的死亡抑制性BH4结构域和人类免疫缺陷病毒Tat蛋白的蛋白质转导结构域组成。这种融合蛋白降低了原代海马培养物中由兴奋性毒素谷氨酸和海藻酸引起的神经毒性，并在兴奋性毒性癫痫模型中减轻了体内海马损伤。
