Mechanism of neurotrophin processing which determines survival or death of neurons

神经营养因子，包括神经生长因子和神经营养因子，不仅以成熟形式分泌，而且以前体形式分泌。这两种形式的神经营养因子对神经元表现出相反的作用，即生存或死亡。因此，从前体到成熟神经营养因子的加工步骤是极其重要的。确定了神经营养因子的分子内序列，确定了神经营养因子的加工效率。2、细胞内影响神经营养因子加工的蛋白质目前正在根据与proNGF的相互作用进行筛选。3.高密度的细胞部分刺激了成熟神经生长因子的产生，尽管成熟神经营养因子前体在细胞外的变化可以忽略不计。为了构建灵敏的proNGF的EIA检测体系，利用DNA重组技术在昆虫细胞中生产了不可切割的proNGF，并制备了其抗体。这种灵敏的EIA分析系统应该是有用的，因为前神经营养因子的产生被认为与神经退行性疾病有关。5、NGF前区域的寡糖被发现对NGF的加工和分泌是必不可少的。目前正在研究寡糖在前肽中的位置对糖基化形式的proNGF在细胞内加工和代谢的影响。6、当NGF及其受体在细胞中共表达时，细胞有死亡的趋势。这表明NGF及其受体发生了细胞内相互作用，其机制目前正在研究中。

Neurotrophins, including NGF and BDNF, are secreted not only as mature forms but also as precursors. The two forms of neurotrophins exhibit opposite effects on neurons, namely survival or death. Therefore, the processing step from precursor to mature neurotrophin is extremely important. Following points have been examined.1, Intramolecular sequence of neurotrophins that determined the processing efficiency was clarified. The C-terminal side of their pro-region was especially effective on their processing.2, Intracellular proteins that affect the neurotrophin processing are now being screened on the basis of the interaction with proNGF.3, The high density of cells stimulated partially the production of mature NGF, although the extracellular change of precursor to mature neurotrophin was negligible with the cultured cells. The expression of processing enzymes by high density cells is now being examined.4, In order to construct sensitive EIA assay system of proNGF, uncleavable proNGF was produced by DNA recombinant technique in the insect cells, and its antibody is now being made. Such a sensitive EIA assay system should be useful since the production of pro-neurotrophins is considered to be linked to neurodegenerative diseases.5, Oligosaccharides in the pro-region of NGF was found to be essential for the processing and secretion of NGF. The effect of the oligosaccharide location in propeptides on the processing and the metabolism of the aglyco-form of proNGF in cells is now being examined.6, When NGF and its receptors were co-expressed in cells, the cells had a tendency to die. This suggests the intracellular interaction of NGF and its receptors occurred, which mechanism is now being examined.