Department of Biology, Tor Vergata University, Rome, Italy.
Front Immunol. 2020 Aug 14;11:1394. doi: 10.3389/fimmu.2020.01394. eCollection 2020.
The process of uncontrolled internal scarring, called fibrosis, is now emerging as a pathological feature shared by both peripheral and central nervous system diseases. In the CNS, damaged neurons are not replaced by tissue regeneration, and scar-forming cells such as endothelial cells, inflammatory immune cells, stromal fibroblasts, and astrocytes can persist chronically in brain and spinal cord lesions. Although this process was extensively described in acute CNS damages, novel evidence indicates the involvement of a fibrotic reaction in chronic CNS injuries as those occurring during neurodegenerative diseases, where inflammation and fibrosis fuel degeneration. In this mini review, we discuss recent advances around the role of fibrotic scar formation and function in different neurodegenerative conditions, particularly focusing on the rising role of scarring in the pathogenesis of amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease and highlighting the therapeutic relevance of targeting fibrotic scarring to slow and reverse neurodegeneration.
不受控制的内部瘢痕形成过程,即纤维化,现在被认为是周围和中枢神经系统疾病共有的病理特征。在中枢神经系统中,受损的神经元不会被组织再生所取代,而内皮细胞、炎症免疫细胞、基质成纤维细胞和星形胶质细胞等形成瘢痕的细胞可以在脑和脊髓损伤中持续存在。尽管这一过程在急性中枢神经系统损伤中被广泛描述,但新的证据表明,纤维化反应参与了慢性中枢神经系统损伤,如神经退行性疾病中发生的损伤,其中炎症和纤维化加剧了变性。在这篇综述中,我们讨论了纤维化瘢痕形成和功能在不同神经退行性疾病中的作用的最新进展,特别是强调了瘢痕形成在肌萎缩侧索硬化症、多发性硬化症和阿尔茨海默病发病机制中的作用,并强调了靶向纤维化瘢痕以减缓和逆转神经退行性变的治疗相关性。