Zhang Linjie, Verkhratsky Alexei, Shi Fu-Dong
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Bizkaia, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
Handb Clin Neurol. 2025;210:133-145. doi: 10.1016/B978-0-443-19102-2.00001-6.
Multiple sclerosis and neuromyelitis optica are autoimmune neurodegenerative diseases primarily targeting myelin sheath and neuroglia. In multiple sclerosis, autoantibodies destroy oligodendrocytes and myelin, which underlies primary neurologic symptoms. Focal damage to myelin triggers reactive astrogliosis and microgliosis, which contribute to and to a large extent define the disease progression. In neuromyelitis optica, autoantibodies against water channel aquaporin 4 (AQP4), which are localized at astrocytic endfeet mediate damage of the glia limitans thus facilitating infiltration of blood-borne molecules and cells that propagate the damage to nerves and neurons. This primary astrocytopathy recruits microglia, which contribute to the neuroinflammatory response. Neuroglial cells therefore are potential targets for cell-specific therapies.
多发性硬化症和视神经脊髓炎是主要针对髓鞘和神经胶质的自身免疫性神经退行性疾病。在多发性硬化症中，自身抗体破坏少突胶质细胞和髓鞘，这是主要神经症状的基础。髓鞘的局灶性损伤引发反应性星形胶质细胞增生和小胶质细胞增生，这在很大程度上促进并决定了疾病的进展。在视神经脊髓炎中，针对水通道蛋白4（AQP4）的自身抗体位于星形胶质细胞终足，介导胶质界膜的损伤，从而促进血源性分子和细胞的浸润，这些分子和细胞将损伤传播至神经和神经元。这种原发性星形细胞病会募集小胶质细胞，从而促成神经炎症反应。因此，神经胶质细胞是细胞特异性疗法的潜在靶点。
