神经营养因子前体蛋白功能的研究进展

Progress in Proneurotrophins Functions

神经营养因子是一组在结构与功能上具有相关性的多肽性因子,它们通过前体蛋白的切割成为具有特定功能的成熟蛋白,为不同的神经细胞亚群提供营养支持,在中枢神经系统和周围神经系统的发育分化及病理生理中起着重要的作用。以前认为神经营养因子的前体不具有生理功能,最近的研究则表明,神经营养因子前体蛋白具有不同于神经营养因子的功能。研究发现,神经营养因子前体,至少神经生长因子和脑源性神经营养因子的前体大量存在于细胞外,它们通过与p75NTR和sortilin受体组成三聚体诱导神经细胞的凋亡。这一机制可能与神经发育时调节神经细胞的比例,神经损伤后神经细胞的死亡以及某些人类疾病的发生有密切联系。此外,神经营养因子前体还可能具有其他未知的新功能,对神经营养因子前体功能的深入研究将使人们对神经系统的发生、发育及神经系统疾病的发病机制有更加深入的了解,并有助于神经系统疾病新药物、新疗法的开发与研究。

Neurotrophins are a group of structurally related polypeptide that provides trophic support for different neuronal subpopulation in the developing and adult nervous system, contributing to the development, maintenance and function of central nervous system and peripheral nervous system. Functional mature neurotrophins were released from their precusors （proneurotrophins） by proteolysis intracellularly or extracellularly. Recent studies show that the proneurotrophins have antagonistic functions with their mature counterparts, in most cases, inducing neuronal apoptosis by p75^NTR/sortilin receptor complex rather than surviving neuronal cells by trophic effect. These results suggested that the proneurotrophins may contribute to adjusting the ratio of neuronal subpopulations in development and inducing neuron death in degeneration or in response to injury in adult. The accumulating data will be helpful to understand the exactly role or pathological mechanism of proneurotrophins in nerve system and may supply new means to develop new drugs for clinical theranv.