IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.

IGF 结合蛋白-2 是发育中和肿瘤神经细胞中 IGF 作用的调节剂。

• 批准号: nhmrc : 209067
• 负责人: Dr Vincenzo Russo
• 金额: $ 29.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/igf-binding-protein-neuronal-cells/77761
• 关键词: IGF; BINDING; PROTEIN; MODULATOR; ACTION

In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.

在生命早期，大脑经历快速生长和重塑，这一过程受到许多因素的调节，包括胰岛素样生长因子 (IGF) 系统，该系统可有效增强神经细胞（神经元）的存活率。同样，该系统对中风等脑损伤做出积极反应，但它也可能提高肿瘤的存活率。神经元 IGF 可用性的调节在所有这些过程中都至关重要。 IGF 结合蛋白 2 (IGFBP-2) 在发育中或受损的大脑以及肿瘤中含量很高，在神经元表面调节 IGF 可用性方面发挥着关键作用。我们已经证明 IGFBP-2 与神经细胞上的一种特殊蛋白质结合，在神经细胞中它被进一步加工成更小的片段。我们相信，这些过程在脑损伤后或 IGFBP-2 高度丰富的癌症状态下会重新激活。我们建议确定 IGFBP-2 如何影响 IGF 在神经细胞表面的作用，并进一步确定该过程中每个步骤的功能。我们将通过检查 IGFBP-2 突变版本的影响来实现这一目标，该突变版本旨在阻止其与细胞表面结合或加工成更小的片段。我们将使用各种人类和小鼠神经细胞进行这些研究，这不仅可以更好地了解 IGF 对发育中脑细胞的可用性的调节，而且还指出这些过程如何参与促进损伤或中风的恢复，或者可能参与加速肿瘤生长。这项研究的发现将为新的、令人兴奋的治疗提供潜力，这些治疗旨在改变 IGF 系统的功能，使其对脑损伤或中风的反应更加活跃，或者在脑肿瘤中降低其活性。