A role for inflammatory RIPK1 signaling in ALS pathogenesis
Motor neuron loss is characteristic of amyotrophic lateral sclerosis (ALS) with the neuroinflammation from activated microglia and astrocytes but how glial cells change and impact ALS pathogenesis is unclear.
The researchers utilize single-nucleus RNA sequencing to identify disease-enriched glial inflammatory states and activation markers in ALS spinal cords.
Using human tissue, iPSC-derived tri-cultures, and the SOD1G93A mouse model, they demonstrate that receptor-interacting protein kinase 1 (RIPK1) signaling is deleterious and identify RIPK1- modulated biomarkers that can be tracked in disease.
The authors show, RIPK1-modulated cytokines are elevated in the CSF of people with ALS and blocking RIPK1 kinase activity delayed symptom onset and motor impairment and modulated glial responses.
https://www.cell.com/immunity/fulltext/S1074-7613%2825%2900091-3
