Kamińska Joanna, Kochański Andrzej
Institute of Biochemistry and Biophysics Polish Academy of Sciences, 02-106 Warsaw, Poland.
Neuromuscular Unit, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warsaw, Poland.
Int J Mol Sci. 2024 Dec 24;26(1):15. doi: 10.3390/ijms26010015.
Despite the fact that there are published case reports and model work providing evidence of inflammation in Charcot-Marie-Tooth disorders (CMTs), in clinical practice, CMT and inflammatory neuropathies are always classified as two separate groups of disorders. This sharp separation of chronic neuropathies into two groups has serious clinical implications. As a consequence, the patients harboring CMT mutations are practically excluded from pharmacological anti-inflammatory treatments. In this review, we present that neuropathological studies of peripheral nerves taken from some patients representing familial aggregation of CMTs revealed the presence of inflammation within the nerves. This shows that neurodegeneration resulting from germline mutations and the inflammatory process are not mutually exclusive. We also point to reports demonstrating that, at the clinical level, a positive response to anti-inflammatory therapy was observed in some patients diagnosed with CMTs, confirming the role of the inflammatory component in CMT. We narrowed a group of more than 100 genes whose mutations were found in CMT-affected patients to the seven most common (, , , , , , and ) as being linked to the coexistence of hereditary and inflammatory neuropathy. We listed studies of mouse models supporting the idea of the presence of an inflammatory process in some CMTs and studies demonstrating at the cellular level the presence of an inflammatory response. In the following, we discuss the possible molecular basis of some neuropathies involving neurodegenerative and inflammatory processes at both the clinical and morphological levels. Finally, we discuss the prospect of a therapeutic approach using immunomodulation in some patients affected by CMTs.
尽管已有发表的病例报告和模型研究提供了夏科-马里-图斯病（CMT）存在炎症的证据，但在临床实践中，CMT和炎性神经病始终被归类为两组不同的疾病。将慢性神经病如此明确地分为两组具有严重的临床意义。因此，携带CMT突变的患者实际上被排除在抗炎药物治疗之外。在本综述中，我们指出，对一些代表CMT家族聚集的患者的周围神经进行神经病理学研究发现，神经内存在炎症。这表明种系突变导致的神经退行性变和炎症过程并非相互排斥。我们还指出有报告表明，在临床层面，一些被诊断为CMT的患者对抗炎治疗有阳性反应，证实了炎症成分在CMT中的作用。我们将在受CMT影响的患者中发现突变的100多个基因缩小到最常见的7个（、、、、、和），这些基因与遗传性和炎性神经病的共存有关。我们列出了支持某些CMT中存在炎症过程这一观点的小鼠模型研究，以及在细胞水平证明存在炎症反应的研究。接下来，我们将在临床和形态学层面讨论一些涉及神经退行性变和炎症过程的神经病的可能分子基础。最后，我们讨论了在一些受CMT影响的患者中使用免疫调节进行治疗的前景。
