How neurons maintain their axons long-term: an integrated view of axon biology and pathology.
How neurons maintain their axons long-term: an integrated view of axon biology and pathology.
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神经元如何长期维持其轴突：轴突生物学和病理学的综合观点。
DOI：
10.3389/fnins.2023.1236815
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发表时间：
2023
影响因子：
4.3
通讯作者：
Prokop, Andreas
中科院分区：
文献类型：
--
作者：
Smith, Gaynor;Sweeney, Sean T.;O'Kane, Cahir J.;Prokop, Andreas
轴突是神经元的突起，长达一米，形成连接神经系统的基本生物电缆。它们必须生存，通常远离细胞体，在人类中长达一个世纪。这需要自给自足的细胞生物学，包括结构蛋白，细胞器和膜运输，代谢，信号传导，翻译，伴侣和降解机制-所有维持能量，脂质，蛋白质和信号网络，包括活性氧和钙的稳态。轴突的维持还涉及专门的细胞骨架，包括皮质肌动蛋白-血影蛋白紧身衣，以及为几乎所有上述过程的组件和细胞器的马达驱动运输提供高速公路的微管束。在这里，我们的目标是提供一个概念性的概述轴突生物学和生理学的关键方面，以及它们形成的稳态网络。这种稳态可能会被破坏，通过衰老、创伤、中毒、炎症或基因突变引起轴突病变。为了说明哪些细胞器或细胞生物学过程的故障可能导致轴突病，我们专注于轴突病相关的亚细胞缺陷引起的基因突变。基于这些描述，并通过我们对与神经疾病相关的基因的全面数据挖掘，我们将“局部轴突稳态的依赖周期”描述为一个综合模型，以解释为什么非常不同的原因可以引发非常相似的轴突病，提供新的想法，可以推动寻求能够对抗这些毁灭性疾病的策略。
Axons are processes of neurons, up to a metre long, that form the essential biological cables wiring nervous systems. They must survive, often far away from their cell bodies and up to a century in humans. This requires self-sufficient cell biology including structural proteins, organelles, and membrane trafficking, metabolic, signalling, translational, chaperone, and degradation machinery—all maintaining the homeostasis of energy, lipids, proteins, and signalling networks including reactive oxygen species and calcium. Axon maintenance also involves specialised cytoskeleton including the cortical actin-spectrin corset, and bundles of microtubules that provide the highways for motor-driven transport of components and organelles for virtually all the above-mentioned processes. Here, we aim to provide a conceptual overview of key aspects of axon biology and physiology, and the homeostatic networks they form. This homeostasis can be derailed, causing axonopathies through processes of ageing, trauma, poisoning, inflammation or genetic mutations. To illustrate which malfunctions of organelles or cell biological processes can lead to axonopathies, we focus on axonopathy-linked subcellular defects caused by genetic mutations. Based on these descriptions and backed up by our comprehensive data mining of genes linked to neural disorders, we describe the ‘dependency cycle of local axon homeostasis’ as an integrative model to explain why very different causes can trigger very similar axonopathies, providing new ideas that can drive the quest for strategies able to battle these devastating diseases.
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影响因子：
16.6
作者：
Ageta-Ishihara, Natsumi;Miyata, Takaki;Ohshima, Chika;Watanabe, Masahiko;Sato, Yoshikatsu;Hamamura, Yuki;Higashiyama, Tetsuya;Mazitschek, Ralph;Bito, Haruhiko;Kinoshita, Makoto
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通讯作者：
Landers, John E.
影响因子：
9.8
作者：
Antonicka, Hana;Ostergaard, Elsebet;Shoubridge, Eric A.
通讯作者：
Shoubridge, Eric A.
影响因子：
3.5
作者：
O'Sullivan NC;Jahn TR;Reid E;O'Kane CJ
通讯作者：
O'Kane CJ
影响因子：
21.3
作者：
Adriaenssens, Elias;Asselbergh, Bob;Rivera-Mejias, Pablo;Bervoets, Sven;Vendredy, Leen;De Winter, Vicky;Spaas, Katrien;de Rycke, Riet;van Isterdael, Gert;Impens, Francis;Langer, Thomas;Timmerman, Vincent
通讯作者：
Timmerman, Vincent