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白细胞介素-3 控制 tau 修饰,并保护皮质神经元免受神经退行性变的影响。

IL-3 controls tau modifications and protects cortical neurons from neurodegeneration.

机构信息

Instituto de Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Isla Teja, Valdivia, Chile.

出版信息

Curr Alzheimer Res. 2010 Nov;7(7):615-24. doi: 10.2174/156720510793499011.

Abstract

Interleukin-3 (IL-3) regulates the proliferation, survival and differentiation of haematopoietic cells via interaction with specific cell-surface receptors. IL-3 is expressed in several non-hematopoietic cell types. Studies have demonstrated the presence of IL-3 in the central nervous system, however, its physiological role in these cells is poorly understood. Previously we have been demonstrated that IL-3 prevents neuronal death induced by fibrillary β amyloid in these cells, by PI 3-kinase and Jak/STAT pathway activation. In this study, we demonstrated that IL-3 significantly reduced Aβ-promoted neurite degeneration and toxicity. Thus, this cytokine provides cellular protection against Aβ neurotoxicity in primary cortical neuronal cells, by modulating microtubular dynamics and prevention of tau cleavage and hyperphosphorylation. We also demonstrates that IL-3 is expressed in the "in vivo" mouse model of AD, Tg2576, which also expresses human AβPP with the Swedish mutation. In summary, these results suggest that IL-3 could play a neuroprotective role in AD.

摘要

白细胞介素-3(IL-3)通过与特定的细胞表面受体相互作用,调节造血细胞的增殖、存活和分化。IL-3在几种非造血细胞类型中表达。研究表明,IL-3存在于中枢神经系统中,但其在这些细胞中的生理作用尚不清楚。我们之前已经证明,IL-3 通过 PI 3-激酶和 Jak/STAT 途径的激活,可防止纤维状β淀粉样蛋白诱导的这些细胞中的神经元死亡。在这项研究中,我们证明了 IL-3 可显著减少 Aβ 诱导的神经突退化和毒性。因此,这种细胞因子通过调节微管动力学和防止 tau 裂解和过度磷酸化,为原代皮质神经元细胞提供了针对 Aβ 神经毒性的细胞保护。我们还证明,IL-3 在表达人 AβPP 瑞典突变的 AD 小鼠模型“体内”Tg2576 中表达。总之,这些结果表明 IL-3 可能在 AD 中发挥神经保护作用。

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