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胰岛素样生长因子系统调节少突胶质细胞行为:在中枢神经系统中的治疗潜力。

Insulin-like growth factor system regulates oligodendroglial cell behavior: therapeutic potential in CNS.

作者信息

Chesik Daniel, De Keyser Jacques, Wilczak Nadine

机构信息

Department of Neurology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

出版信息

J Mol Neurosci. 2008 May;35(1):81-90. doi: 10.1007/s12031-008-9041-2. Epub 2008 Feb 26.

Abstract

Amongst the many soluble extracellular factors stimulating intracellular signal transduction pathways and driving cellular processes such as proliferation, differentiation and survival, insulin-like growth factors (IGFs) stand out as indispensable factors for proper oligodendrocyte differentiation and accompanying myelin production. Owing to its potent myelinogenic capacity and its neuroprotective properties, IGFs hold therapeutic potential in demyelinating and neurodengenerative diseases. However, the IGF system is comprised of a complex molecular network involving regulatory binding proteins, proteases, cell surface and extracellular matrix components which orchestrate IGF-specific functions. Thus, the complexity by which these factors are tightly regulated makes a simplistic therapeutic approach towards treating demyelinating conditions unfeasible. In the present review, we address these issues and consider current therapeutic prospects of oligodendrocyte-targeted IGF-based therapies.

摘要

在众多刺激细胞内信号转导通路并驱动细胞增殖、分化和存活等过程的可溶性细胞外因子中,胰岛素样生长因子(IGFs)是少突胶质细胞正常分化及伴随的髓鞘生成所不可或缺的因子。由于其强大的髓鞘生成能力和神经保护特性,IGFs在脱髓鞘疾病和神经退行性疾病中具有治疗潜力。然而,IGF系统由一个复杂的分子网络组成,涉及调节性结合蛋白、蛋白酶、细胞表面和细胞外基质成分,这些成分共同协调IGF的特定功能。因此,这些因子受到严格调控的复杂性使得针对脱髓鞘疾病的简单治疗方法不可行。在本综述中,我们将探讨这些问题,并考虑以少突胶质细胞为靶点的基于IGF的治疗方法的当前治疗前景。

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