Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found in affected brain regions, but how iron accumulation influences microglia physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived microglia grown in a tri-culture system are highly responsive to iron and susceptible to ferroptosis, an iron-dependent form of cell death. Furthermore, iron overload causes a marked shift in the microglial transcriptional state that overlaps with a transcriptomic signature found in PD postmortem brain microglia. Our data also show that this microglial…

• MJ
  Michael J. Fox Foundation for Parkinson's Research
• P
  Pfizer
• G
  GlaxoSmithKline
• S
  Sanofi
• C
  Celgene
• VL
  Verily Life Sciences
• NI
  National Institutes of Health
• NI
  National Institute of Neurological Disorders and Stroke