Twiss Jeffery L, Buchanan Courtney N
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Carolina Autism and Neurodevelopment Research Center, McCausland College of Arts and Sciences, University of South Carolina, Columbia, SC 20208, USA.
Int J Mol Sci. 2025 Jul 28;26(15):7283. doi: 10.3390/ijms26157283.
Neuronal proteins synthesized locally in axons and dendrites contribute to growth, plasticity, survival, and retrograde signaling underlying these cellular processes. Advances in molecular tools to profile localized mRNAs, along with single-molecule detection approaches for RNAs and proteins, have significantly expanded our understanding of the diverse proteins produced in subcellular compartments. These investigations have also uncovered key molecular mechanisms that regulate mRNA transport, storage, stability, and translation within neurons. The long distances that axons extend render their processes vulnerable, especially when injury necessitates regeneration to restore connectivity. Localized mRNA translation in axons helps initiate and sustain axon regeneration in the peripheral nervous system and promotes axon growth in the central nervous system. Recent and ongoing studies suggest that axonal RNA transport, storage, and stability mechanisms represent promising targets for enhancing regenerative capacity. Here, we summarize critical post-transcriptional regulatory mechanisms, emphasizing translation in the axonal compartment and highlighting potential strategies for the development of new regeneration-promoting therapeutics.
在轴突和树突中局部合成的神经元蛋白质有助于这些细胞过程背后的生长、可塑性、存活和逆行信号传导。用于分析局部mRNA的分子工具的进展，以及用于RNA和蛋白质的单分子检测方法，显著扩展了我们对亚细胞区室中产生的多种蛋白质的理解。这些研究还揭示了调节神经元内mRNA运输、储存、稳定性和翻译的关键分子机制。轴突延伸的长距离使其过程容易受到伤害，尤其是当损伤需要再生以恢复连接时。轴突中的局部mRNA翻译有助于在外周神经系统中启动和维持轴突再生，并促进中枢神经系统中的轴突生长。最近和正在进行的研究表明，轴突RNA运输、储存和稳定性机制是增强再生能力的有希望的靶点。在这里，我们总结关键的转录后调控机制，强调轴突区室中的翻译，并突出开发新的促进再生疗法的潜在策略。
