Maragakis Nicholas J, Rothstein Jeffrey D
Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer 6-119, Baltimore, MD 21287, USA.
Nat Clin Pract Neurol. 2006 Dec;2(12):679-89. doi: 10.1038/ncpneuro0355.
The term neurodegenerative disease refers to the principal pathology associated with disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease and Parkinson's disease, and it is presumed that neurodegeneration results in the clinical findings seen in patients with these diseases. Decades of pathological and physiological studies have focused on neuronal abnormalities in these disorders, but it is becoming increasingly evident that astrocytes are also important players in these and other neurological disorders. Our understanding of the normative biology of astrocytes has been aided by the development of animal models in which astrocyte-specific proteins and pathways have been manipulated, and mouse models of neurodegenerative diseases have also revealed astrocyte-specific pathologies that contribute to neurodegeneration. These models have led to the development of targeted therapies for pathways in which astrocytes participate, and this research should ultimately influence the clinical treatment of neurodegenerative disorders.
神经退行性疾病这一术语指的是与肌萎缩侧索硬化症、阿尔茨海默病、亨廷顿舞蹈症和帕金森病等疾病相关的主要病理学特征,据推测神经退行性变导致了这些疾病患者出现的临床症状。数十年来的病理学和生理学研究聚焦于这些疾病中的神经元异常,但越来越明显的是,星形胶质细胞在这些及其他神经系统疾病中也是重要参与者。对星形胶质细胞正常生物学特性的理解得益于动物模型的开发,在这些模型中,星形胶质细胞特异性蛋白和信号通路已被操控,神经退行性疾病的小鼠模型也揭示了有助于神经退行性变的星形胶质细胞特异性病理学特征。这些模型促使了针对星形胶质细胞参与的信号通路的靶向治疗的开发,并且这项研究最终应会影响神经退行性疾病的临床治疗。