2025/02/26 by Selena E. Romero, Matthew J Geden, Richa Basundra +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Immune Response and Inflammation #Inflammasome and immune disorders #interferon and immune responses
paper · doi:10.1038/s44319-025-00402-y
openalex publication_date 2025/02/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
Axon pruning is a unique process neurons utilize to selectively degenerate axon branches while keeping the neuronal cell body intact. The mechanisms of axon pruning have much in common with those of apoptosis. Both axon pruning and apoptosis pathways require key apoptotic proteins (Bax, Caspase-9, Caspase-3). Interestingly, axon pruning does not require Apaf-1, a key member of the apoptosome complex. As such, exactly how caspases are activated in an apoptosome-independent manner during axon pruning is unknown. Here we show that neurons utilize the NLRP1 inflammasome, an innate immune sensor of pathogens, specifically for axon pruning. Strikingly, NLRP1b-deficient neurons were unable to prune axons both in vitro and in vivo, but fully capable of degenerating during apoptosis. Our results reveal NLRP1 as an immune molecule engaged by neurons for an unexpected physiological function independent of its pathogen-induced proinflammatory role.