Grassi Sara, Prinetti Alessandro
Department of Medical Biotechnology and Translational Medicine, Via Fratelli Cervi 93, 20090 Segrate (Milano),University of Milan, Milan, Italy.
Biochem Soc Trans. 2025 Jun 30;53(3):653-669. doi: 10.1042/BST20231085.
Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions characterized by heterogeneous and sometimes disease-specific etiopathological mechanisms. While several approaches aimed at ameliorating the symptoms and the progression of some of these diseases exist, the most effective cure for all demyelinating diseases would be regeneration of lost myelin. Myelin regeneration occurs spontaneously in the central nervous system in response to myelin damage but is inefficient for a variety of reasons, especially in human patients. In this review, we will discuss the contributions of different cell populations to the creation of conditions permissive for effective remyelination and to the formation of new myelin after injury. Moreover, we would like to highlight the importance of sphingolipids in the network of interactions between these cell populations. Mutations in genes encoding sphingolipid metabolic enzymes (such as GALC) represent a major risk factor for multiple sclerosis, and alterations in sphingolipid metabolism in specific cell types contribute to myelin damage. On the other hand, sphingolipid signaling, in particular through sphingosine 1 phosphate, directly affects the process of myelin regeneration, with distinct effects on different cellular populations.
每10万人中约有35人受与髓鞘丢失相关的疾病影响，这些疾病通常被称为脱髓鞘疾病。脱髓鞘疾病涵盖许多不同的病理状况，其特征是病因病理机制具有异质性，有时还具有疾病特异性。虽然存在几种旨在缓解其中一些疾病的症状和进展的方法，但对所有脱髓鞘疾病最有效的治疗方法是再生丢失的髓鞘。髓鞘再生在中枢神经系统中会因髓鞘损伤而自发发生，但由于各种原因效率低下，尤其是在人类患者中。在本综述中，我们将讨论不同细胞群对创造有利于有效髓鞘再生的条件以及损伤后新髓鞘形成的贡献。此外，我们想强调鞘脂在这些细胞群之间相互作用网络中的重要性。编码鞘脂代谢酶（如GALC）的基因突变是多发性硬化症的主要危险因素，特定细胞类型中鞘脂代谢的改变会导致髓鞘损伤。另一方面，鞘脂信号传导，特别是通过1-磷酸鞘氨醇，直接影响髓鞘再生过程，对不同细胞群有不同影响。
