Astrocytes a predominant glial population in the human central nervous system, normallyplay critical roles in neuroprotection, immunity, and homeostasis. However,upon exposure to specific neuroinflammatory cues, astrocytes assume apro-inflammatory, neurotoxic phenotype. Neurotoxic astrocytes promote chronic neuro inflammation, a common driver of many neurodegenerative diseases.

Identifying and targeting the signalling pathways that lead to the formation of neurotoxic astrocytes can provide novel therapeutic approaches to curb neurodegeneration. The preclinical development of new drugs targeting neurotoxic astrocytes requires scalable, robust and reproducible assays that harness accurate, translational and accessible invitro models of the neurotoxic phenotype. Here, we aimed to assess the validity of commercially available human iPSC-derived astrocytes exposed to neuroinflammatory stimuli as a representative model of reactive neurotoxic astrocytes.

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