Examining the relationship between astrocyte dysfunction and neurodegeneration in ALS using hiPSCs

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.