A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.
A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.
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DOI：
10.3389/fnins.2017.00481
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发表时间：
2017
影响因子：
4.3
通讯作者：
Segal RA
中科院分区：
文献类型：
--
作者：
Fukuda Y;Li Y;Segal RA
化疗药物会对周围神经系统（PNS）产生许多短期和长期的毒副作用，从而大大改变患者的生活质量。化疗诱导的周围神经病变（CIPN）是由多种抗肿瘤药物引起的一种常见且持久的疾病。CIPN通常表现为神经性疼痛，远端肢体麻木，和/或对热或机械刺激过度敏感。这种不良副作用通常需要减少化疗剂量甚至停止治疗。目前CIPN没有有效的治疗方案。虽然CIPN的潜在机制尚不清楚，但目前的数据表明，远端神经末梢的“死后”轴突变性是该疾病的主要病理。因此，对轴突退化的机制理解将提供对负责CIPN的途径和分子参与者的见解。在这里，我们回顾了最近的发现，这些发现扩大了我们对CIPN发病机制的理解，并讨论了在发育轴突修剪和损伤诱导的沃勒氏变性过程中发生的轴突变性可能与之共享的途径。这些机制的见解为开发预防或治疗CIPN的疗法提供了新的途径。
Chemotherapeutic agents cause many short and long term toxic side effects to peripheral nervous system (PNS) that drastically alter quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to thermal or mechanical stimuli. This adverse side effect often requires a reduction in chemotherapy dosage or even discontinuation of treatment. Currently there are no effective treatment options for CIPN. While the underlying mechanisms for CIPN are not understood, current data identify a “dying back” axon degeneration of distal nerve endings as the major pathology in this disorder. Therefore, mechanistic understanding of axon degeneration will provide insights into the pathway and molecular players responsible for CIPN. Here, we review recent findings that expand our understanding of the pathogenesis of CIPN and discuss pathways that may be shared with the axonal degeneration that occurs during developmental axon pruning and during injury-induced Wallerian degeneration. These mechanistic insights provide new avenues for development of therapies to prevent or treat CIPN.
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DOI：
10.1523/jneurosci.3347-10.2011
发表时间：
2011-02-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Courchesne SL;Karch C;Pazyra-Murphy MF;Segal RA
通讯作者：
Segal RA
影响因子：
--
作者：
Addington, James;Freimer, Miriam
通讯作者：
Freimer, Miriam
影响因子：
2.9
作者：
Cata, Juan P.;Weng, Han-Rong;Dougherty, Patrick M.
通讯作者：
Dougherty, Patrick M.
影响因子：
5.3
作者：
Cavaletti, Guido;Gilardini, Alessandra;De Coster, Roland
通讯作者：
De Coster, Roland
影响因子：
25
作者：
Cosker KE;Fenstermacher SJ;Pazyra-Murphy MF;Elliott HL;Segal RA
通讯作者：
Segal RA