Age-related loss of axonal regeneration is reflected by the level of local translation.
Age-related loss of axonal regeneration is reflected by the level of local translation.
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DOI：
10.1016/j.expneurol.2020.113594
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Ffrench-Constant C
中科院分区：
文献类型：
--
作者：
van Erp S;van Berkel AA;Feenstra EM;Sahoo PK;Wagstaff LJ;Twiss JL;Fawcett JW;Eva R;Ffrench-Constant C
再生能力随着中枢神经系统轴突的成熟而降低。利用激光介导的轴突切开术、蛋白质组学和基于嘌呤霉素的标记人类胚胎干细胞衍生的神经元培养系统中新合成的蛋白质，可以从细胞体中分离轴突，我们在这里表明，年轻轴突的有效再生（培养d45）与局部轴突蛋白合成（局部翻译）有关。与人胶质前体细胞共培养可促进再生，与轴突蛋白质合成增加有关，包括那些构成翻译机制本身的蛋白质。随着这些轴突在培养中d65成熟，再生减少与参与翻译的轴突蛋白水平降低有关，并且无法通过增加从应激颗粒中释放的促进再生的轴突mrna的翻译来做出反应。总之，我们的研究结果提供了证据，证明在发育和PNS中，局部翻译有助于中枢神经系统轴突再生。激光介导的hesc源性神经元轴突切开术被用作轴突再生和局部蛋白质翻译的模型。新合成的轴突蛋白Pull - down用于识别轴突损伤后局部蛋白的合成。轴突再生减少与局部翻译水平降低有关。通过与人类胶质前体细胞共培养来增强再生与提高翻译水平有关。衰老过程中轴突蛋白质的蛋白质组学分析揭示了随着轴突年龄的增长蛋白质翻译机制的减少。
Regeneration capacity is reduced as CNS axons mature. Using laser-mediated axotomy, proteomics and puromycin-based tagging of newly-synthesized proteins in a human embryonic stem cell-derived neuron culture system that allows isolation of axons from cell bodies, we show here that efficient regeneration in younger axons (d45 in culture) is associated with local axonal protein synthesis (local translation). Enhanced regeneration, promoted by co-culture with human glial precursor cells, is associated with increased axonal synthesis of proteins, including those constituting the translation machinery itself. Reduced regeneration, as occurs with the maturation of these axons by d65 in culture, correlates with reduced levels of axonal proteins involved in translation and an inability to respond by increased translation of regeneration promoting axonal mRNAs released from stress granules. Together, our results provide evidence that, as in development and in the PNS, local translation contributes to CNS axon regeneration. Laser-mediated axotomy of hESC-derived neurons is used as a model for axonal regeneration and local protein translation. Pull down of newly synthesized axonal proteins is used to identify local protein synthesis following axonal injury. Reduced axonal regeneration is associated with reduced levels of local translation. Enhancing regeneration by co-culturing with human glial precursor cells is associated with enhanced levels of translation. Proteomics profiling of axonal proteins during aging reveals reduced protein translation machinery as axons age.
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选择性rab11转运和中枢神经系统轴突的内在再生能力。
影响因子：
7.7
作者：
Koseki H;Donegá M;Lam BY;Petrova V;van Erp S;Yeo GS;Kwok JC;Ffrench-Constant C;Eva R;Fawcett JW
通讯作者：
Fawcett JW
DOI：
10.1074/mcp.m111.011015
发表时间：
2011-09
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Michalski A;Damoc E;Hauschild JP;Lange O;Wieghaus A;Makarov A;Nagaraj N;Cox J;Mann M;Horning S
通讯作者：
Horning S
影响因子：
4.5
作者：
Gumy, Laura F.;Yeo, Giles S. H.;Fawcett, James W.
通讯作者：
Fawcett, James W.
影响因子：
5.3
作者：
Deng, Suhua;Hirschberg, Alexandra;Kuner, Rohini
通讯作者：
Kuner, Rohini
检查脊髓损伤中神经胶质限制前体的特性和治疗潜力。
影响因子：
6.1
作者：
Hayakawa K;Haas C;Fischer I
通讯作者：
Fischer I