Abstract：
Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.
摘要：
神经营养因子不仅对于指导发育中的神经系统的组织至关重要，而且对于支持创伤性损伤后神经元的存活和生长也至关重要。在中枢神经系统（CNS），抑制因素和损伤后胶质瘢痕的形成阻碍了神经元的功能恢复，需要外源性疗法来促进再生。Netrin-1是一种神经营养因子,可以启动轴突引导，生长,和分支，以及突触发生，通过激活结直肠癌（DCC）受体缺失。我们在此报告了netrin-1的纳米纤维状超分子模拟物的开发，其单体掺入了环状肽序列作为生物活性成分。发现模拟结构使用低摩尔比的生物活性共聚单体激活初级皮质神经元中的DCC受体。随着时间的推移，超分子纳米纤维增强了神经突生长和上调的成熟以及突触前和突触后标志物，导致与用重组netrin-1蛋白处理的神经元相似的电活动差异。结果表明，使用超分子结构作为治疗剂以促进CNS损伤中的再生生物活性的可能性。
