Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Department of Prenatal Screening and Diagnosis Center, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
Clin Sci (Lond). 2024 Nov 6;138(21):1377-1394. doi: 10.1042/CS20241658.
Neurodegenerative diseases (NDs) involve the progressive loss of neuronal structure or function in the brain and spinal cord. Despite their diverse etiologies, NDs manifest similar pathologies. Emerging research identifies vascular defects as a previously neglected hallmark of NDs. The development and popularization of single-cell RNA sequencing (scRNA-seq) technologies have significantly advanced our understanding of brain vascular cell types and their molecular characteristics, including gene expression changes at the single-cell level in NDs. These unprecedented insights deepen our understanding of the pathogenic mechanisms underlying NDs. However, the occurrence and role of vascular defects in disease progression remain largely unexplored. In this paper, we systematically summarize recent advances in the structure and organization of the central nervous system vasculature in mice, healthy individuals, and patients with NDs, focussing primarily on disease-specific alterations in vascular cell types or subtypes. Combining scRNA-seq with pathology evidence, we propose that vascular defects, characterized by disruptions in cell types and structural integrity, may serve as common early features of NDs. Finally, we discuss several pathways through which vascular defects in NDs lead to neuronal degeneration. A deeper understanding of the causes and contributions of vascular defects to NDs aids in elucidating the pathogenic mechanisms and developing meaningful therapeutic interventions.
神经退行性疾病（NDs）涉及大脑和脊髓中神经元结构或功能的进行性丧失。尽管它们的病因多种多样，但 NDs 表现出相似的病理学特征。新兴研究将血管缺陷确定为 NDs 以前被忽视的标志之一。单细胞 RNA 测序（scRNA-seq）技术的发展和普及极大地提高了我们对脑血管细胞类型及其分子特征的认识，包括 NDs 中单细胞水平的基因表达变化。这些前所未有的见解加深了我们对 NDs 发病机制的理解。然而，血管缺陷在疾病进展中的发生和作用在很大程度上仍未得到探索。在本文中，我们系统地总结了近年来在小鼠、健康个体和 NDs 患者的中枢神经系统血管结构和组织方面的最新进展，主要集中在血管细胞类型或亚型的特异性疾病改变上。我们通过将 scRNA-seq 与病理学证据相结合，提出血管缺陷（以细胞类型和结构完整性的破坏为特征）可能作为 NDs 的常见早期特征。最后，我们讨论了 NDs 中血管缺陷导致神经元变性的几种途径。更深入地了解血管缺陷对 NDs 的原因和贡献有助于阐明发病机制并开发有意义的治疗干预措施。
