Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Neurobiol Dis. 2019 Dec;132:104562. doi: 10.1016/j.nbd.2019.104562. Epub 2019 Aug 2.
Amyotrophic lateral sclerosis (ALS) is a complex and fatal neurodegenerative disease for which the causes of disease onset and progression remain unclear. Recent advances in human induced pluripotent stem cell (hiPSC)-based models permit the study of the genetic factors associated with ALS in patient-derived neural cell types, including motor neurons and glia. While astrocyte dysfunction has traditionally been thought to exacerbate disease progression, astrocytic dysfunction may play a more direct role in disease initiation and progression. Such non-cell autonomous mechanisms expand the potential targets of therapeutic intervention, but only a handful of ALS risk-associated genes have been examined for their impact on astrocyte dysfunction and neurodegeneration. This review summarizes what is currently known about astrocyte function in ALS and suggests ways in which hiPSC-based models can be used to more effectively study the role of astrocytes in neurodegenerative disease.
肌萎缩侧索硬化症（ALS）是一种复杂且致命的神经退行性疾病，其发病和进展的原因尚不清楚。基于人诱导多能干细胞（hiPSC）的模型的最新进展允许研究与 ALS 相关的遗传因素在患者来源的神经细胞类型中，包括运动神经元和神经胶质细胞。虽然星形胶质细胞功能障碍传统上被认为会加剧疾病进展，但星形胶质细胞功能障碍可能在疾病的起始和进展中起更直接的作用。这种非细胞自主机制扩大了治疗干预的潜在靶点，但只有少数与 ALS 相关的风险基因被研究过其对星形胶质细胞功能障碍和神经退行性变的影响。本综述总结了目前关于 ALS 中星形胶质细胞功能的知识，并提出了利用基于 hiPSC 的模型更有效地研究星形胶质细胞在神经退行性疾病中的作用的方法。
