Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein asymmetry can be achieved by the transport of the protein itself or the transport of the mRNA that is then translated at target sites in neuronal processes. The latter transport mechanism implies that protein expression is achieved by translation of localized mRNAs. The role of local translation in nervous system (NS) development and maintenance is well established, but recently there is growing evidence that this mechanism and its deregulation are also relevant in NS pathologies, including neurodegenerative diseases. For instance, upon pathological signals disease-related proteins can be locally synthesized in dendrites and axons. Locally synthesized proteins can exert their effects at or close to the site of translation, or they can be delivered to distal compartments like the nucleus and induce transcriptional responses that lead to neurodegeneration, nerve regeneration and other cell-wide responses. Relevant key players in the process of local protein synthesis are the RNA binding proteins (RBPs), responsible for mRNA transport to neurites. Several neurological and neurodegenerative disorders, including amyotrophic lateral sclerosis or spinal motor atrophy, are characterized by mutations in genes encoding for RBPs and consequently mRNA localization and local translation are impaired. In other diseases changes in the local mRNA repertoire and altered local protein synthesis have been reported. In this review, we will discuss how deregulation of localized translation at different levels can contribute to the development and progression of nervous system pathologies.

中文翻译：

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神经系统病理学中的局部翻译

树突和轴突可以从细胞体延伸几十到几百厘米，这样单个神经元就可以感知和响应数千种刺激。因此，为了树突和轴突的准确功能，神经元蛋白质组需要在神经元内不对称分布。蛋白质不对称可以通过蛋白质本身的运输或 mRNA 的运输来实现，然后在神经元过程的靶位点翻译。后一种转运机制意味着蛋白质表达是通过定位 mRNA 的翻译来实现的。局部翻译在神经系统 (NS) 发育和维持中的作用已得到公认，但最近越来越多的证据表明，这种机制及其失调也与神经系统病理学有关，包括神经退行性疾病。例如，根据病理信号，疾病相关蛋白可以在树突和轴突中局部合成。局部合成的蛋白质可以在翻译位点处或附近发挥作用，或者它们可以传递到细胞核等远端区室并诱导导致神经变性、神经再生和其他全细胞反应的转录反应。局部蛋白质合成过程中的相关关键参与者是 RNA 结合蛋白 (RBP)，负责将 mRNA 转运到神经突。几种神经和神经退行性疾病，包括肌萎缩侧索硬化或脊髓运动萎缩，其特征是编码 RBP 的基因发生突变，因此 mRNA 定位和局部翻译受损。在其他疾病中，已经报道了局部 mRNA 库的变化和局部蛋白质合成的改变。在这篇综述中，我们将讨论在不同层次上对本地化翻译的放松管制如何促进神经系统病理学的发展和进展。