Sosunov Alexander, Olabarria Markel, Goldman James E
Department of Neurosurgery, Columbia University, New York, NY.
Departments of Pathology and Cell Biology, Columbia University, New York, NY.
Brain Pathol. 2018 May;28(3):388-398. doi: 10.1111/bpa.12601.
Alexander Disease (AxD) is a degenerative disorder caused by mutations in the GFAP gene, which encodes the major intermediate filament of astrocytes. As other cells in the CNS do not express GFAP, AxD is a primary astrocyte disease. Astrocytes acquire a large number of pathological features, including changes in morphology, the loss or diminution of a number of critical astrocyte functions and the activation of cell stress and inflammatory pathways. AxD is also characterized by white matter degeneration, a pathology that has led it to be included in the "leukodystrophies." Furthermore, variable degrees of neuronal loss take place. Thus, the astrocyte pathology triggers alterations in other cell types. Here, we will review the neuropathology of AxD and discuss how a disease of astrocytes can lead to severe pathologies in non-astrocytic cells. Our knowledge of the pathophysiology of AxD will also lead to a better understanding of how astrocytes interact with other CNS cells and how astrocytes in the gliosis that accompanies many neurological disorders can damage the function and survival of other cells.
亚历山大病（AxD）是一种由GFAP基因突变引起的退行性疾病，该基因编码星形胶质细胞的主要中间丝。由于中枢神经系统中的其他细胞不表达GFAP，所以AxD是一种原发性星形胶质细胞疾病。星形胶质细胞出现大量病理特征，包括形态改变、一些关键星形胶质细胞功能的丧失或减弱以及细胞应激和炎症信号通路的激活。AxD的另一个特征是白质变性，这种病理特征使其被归入“脑白质营养不良”。此外，还会发生不同程度的神经元丢失。因此，星形胶质细胞病变会引发其他细胞类型的改变。在这里，我们将回顾AxD的神经病理学，并讨论星形胶质细胞疾病如何导致非星形胶质细胞出现严重病变。我们对AxD病理生理学的了解也将有助于更好地理解星形胶质细胞如何与中枢神经系统中的其他细胞相互作用，以及伴随许多神经系统疾病的胶质增生中的星形胶质细胞如何损害其他细胞的功能和存活。
