Corredor Raul G, Goldberg Jeffrey L
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, FL 33136, USA.
J Neural Eng. 2009 Oct;6(5):055001. doi: 10.1088/1741-2560/6/5/055001. Epub 2009 Sep 1.
The failure of regeneration in the central nervous system (CNS) remains an enormous scientific and clinical challenge. After injury or in degenerative diseases, neurons in the adult mammalian CNS fail to regrow their axons and reconnect with their normal targets, and furthermore the neurons frequently die and are not normally replaced. While significant progress has been made in understanding the molecular basis for this lack of regenerative ability, a second approach has gained momentum: replacing lost neurons or lost connections with artificial electrical circuits that interface with the nervous system. In the visual system, gene therapy-based 'optogenetics' prostheses represent a competing technology. Now, the two approaches are converging, as recent data suggest that electrical activity itself, via the molecular signaling pathways such activity stimulates, is sufficient to induce neuronal survival and regeneration, particularly in retinal ganglion cells. Here, we review these data, discuss the effects of electrical activity on neurons' molecular signaling pathways and propose specific mechanisms by which exogenous electrical activity may be acting to enhance survival and regeneration.
中枢神经系统（CNS）再生失败仍然是一个巨大的科学和临床挑战。在受伤或患有退行性疾病后，成年哺乳动物中枢神经系统中的神经元无法再生其轴突并与正常靶点重新连接，此外，神经元经常死亡且通常无法被替代。虽然在理解这种缺乏再生能力的分子基础方面已经取得了重大进展，但另一种方法也获得了发展势头：用与神经系统相连的人工电路替代丢失的神经元或丢失的连接。在视觉系统中，基于基因治疗的“光遗传学”假体代表了一种竞争技术。现在，这两种方法正在融合，因为最近的数据表明，电活动本身通过其刺激的分子信号通路，足以诱导神经元存活和再生，特别是在视网膜神经节细胞中。在这里，我们回顾这些数据，讨论电活动对神经元分子信号通路的影响，并提出外源性电活动可能通过其作用来增强存活和再生的具体机制。
