Mechanisms of distal axonal degeneration in peripheral neuropathies.

Mechanisms of distal axonal degeneration in peripheral neuropathies.
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外周神经病中轴突变性的机制。

DOI:
10.1016/j.neulet.2015.01.048
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发表时间:
2015-06-02
影响因子:
2.5
通讯作者:
Höke A
Höke A
中科院分区:
医学4区
文献类型:
--
作者:
Cashman CR;Höke A

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周围神经病变是多种疾病和治疗的常见并发症,包括糖尿病、癌症化疗和感染原因(HIV、丙型肝炎和空肠弯曲菌)。尽管这些损伤之间存在根本差异,但周围神经病变的发展仅为六种主要机制的组合:代谢改变、共价修饰、细胞器功能和活性氧形成改变、细胞内和炎症信号传导改变、轴突运输减慢以及离子通道动力学和表达改变。所有这些途径汇聚导致轴突功能障碍和神经病变的症状。轴突变性本身的详细机制已经开始通过具有改变的变性动力学的动物模型的研究来阐明,包括减慢的沃勒变性(Wlds)和Sarmknockout动物模型。这些研究表明,轴突变性是通过损伤信号传导和细胞骨架降解的程序化途径发生的。对轴突变性通路上常见疾病损伤的深入了解有望促进可能有效对抗其他神经变性机制的治疗方法的发展。
Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration.
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