Lessons from Injury: How Nerve Injury Studies Reveal Basic Biological Mechanisms and Therapeutic Opportunities for Peripheral Nerve Diseases.
Lessons from Injury: How Nerve Injury Studies Reveal Basic Biological Mechanisms and Therapeutic Opportunities for Peripheral Nerve Diseases.
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DOI：
10.1007/s13311-021-01125-3
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Coleman MP
中科院分区：
文献类型：
--
作者：
Arthur-Farraj P;Coleman MP
自19世纪和20世纪初Waller和Cajal以来，实验室创伤性周围神经损伤研究已经为支配轴突变性和周围神经的主要胶质细胞类型Schwann细胞的反应的细胞和分子机制提供了很好的见解。现在很明显，损伤诱导的轴突变性和雪旺细胞损伤特异性状态，修复雪旺细胞的潜在途径与周围神经的许多遗传性和获得性疾病有关。本文就轴突变性和修复性雪旺细胞形成的分子机制作一综述。我们讨论了烟酰胺单核苷酸腺苷酰转移酶2（NMNAT 2）和无菌α TIR基序包含蛋白1（SARM 1）是需要轴突的生存和变性，分别如何转录因子c-JUN是必不可少的雪旺细胞对神经损伤的反应，以及每个告诉我们的疾病机制和潜在的治疗方法。人类与NMNAT 2和SARM 1的遗传关联分别强烈提示了多发性神经病和运动神经元疾病中程序性轴突死亡的异常激活，动物研究表明了更广泛的参与，包括化疗诱导的和糖尿病性神经病。在修复雪旺细胞中，cJUN在多种人类获得性和遗传性神经病中异常表达。动物模型表明，它限制了遗传性和创伤性神经病中的轴突损失，而相比之下，施万细胞分泌的1型神经调节蛋白-1驱动CMT 1A中的洋葱球病理。最后，我们讨论了基于药物和基因治疗的机会，以防止轴突损失或操纵修复雪旺细胞状态，以治疗获得性和遗传性神经病和神经元病。在线版本包含补充材料，可通过10.1007/s13311-021-01125-3获得。
Since Waller and Cajal in the nineteenth and early twentieth centuries, laboratory traumatic peripheral nerve injury studies have provided great insight into cellular and molecular mechanisms governing axon degeneration and the responses of Schwann cells, the major glial cell type of peripheral nerves. It is now evident that pathways underlying injury-induced axon degeneration and the Schwann cell injury-specific state, the repair Schwann cell, are relevant to many inherited and acquired disorders of peripheral nerves. This review provides a timely update on the molecular understanding of axon degeneration and formation of the repair Schwann cell. We discuss how nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) and sterile alpha TIR motif containing protein 1 (SARM1) are required for axon survival and degeneration, respectively, how transcription factor c-JUN is essential for the Schwann cell response to nerve injury and what each tells us about disease mechanisms and potential therapies. Human genetic association with NMNAT2 and SARM1 strongly suggests aberrant activation of programmed axon death in polyneuropathies and motor neuron disorders, respectively, and animal studies suggest wider involvement including in chemotherapy-induced and diabetic neuropathies. In repair Schwann cells, cJUN is aberrantly expressed in a wide variety of human acquired and inherited neuropathies. Animal models suggest it limits axon loss in both genetic and traumatic neuropathies, whereas in contrast, Schwann cell secreted Neuregulin-1 type 1 drives onion bulb pathology in CMT1A. Finally, we discuss opportunities for drug-based and gene therapies to prevent axon loss or manipulate the repair Schwann cell state to treat acquired and inherited neuropathies and neuronopathies. The online version contains supplementary material available at 10.1007/s13311-021-01125-3.
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DOI：
10.1523/jneurosci.3481-16.2017
发表时间：
2017-04-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Benito C;Davis CM;Gomez-Sanchez JA;Turmaine M;Meijer D;Poli V;Mirsky R;Jessen KR
通讯作者：
Jessen KR
影响因子：
25
作者：
Babetto E;Wong KM;Beirowski B
通讯作者：
Beirowski B
影响因子：
6.2
作者：
Arthur-Farraj, Peter;Moyon, Sarah
通讯作者：
Moyon, Sarah
影响因子：
5.3
作者：
Babetto, Elisabetta;Beirowski, Bogdan;Coleman, Michael P.
通讯作者：
Coleman, Michael P.
影响因子：
14.5
作者：
Antonio Gomez-Sanchez, Jose;Gomis-Coloma, Clara;Cabedo, Hugo
通讯作者：
Cabedo, Hugo