Elucidating the Role of NLRP1 in Axon Pruning of Sympathetic Neurons

During development of the nervous system, neurons undergo axon pruning to selectively degrade their axons to refine connections, while keeping the soma intact. This process relies on similar upstream proteins and a caspase-mediated degradation mechanism like apoptosis. We previously found that axon pruning undergoes an apoptosome-independent mechanism to activate caspases. To explore this discrepancy, we studied the role of various pyroptotic proteins in axon pruning. We utilized a microfluidic model and immunofluorescence to assess axon pruning in sympathetic neurons lacking different inflammasome machinery. We found that NOD-like receptor pyrin domain containing 1 (NLRP1) and Caspase-1 (Casp1) are required for axon pruning, using this model. Canonically, the NLRP1 inflammasome is known to activate Casp1 during pyroptosis in an immunological response, though the role of these molecules in physiological axon pruning is unknown. We investigated the localization of NLRP1 using immunofluorescence and overexpression techniques to show that NLRP1 is localized to the somas of sympathetic neuron. Further studies into the function of NLRP1 and additional key players would uncover the mechanism of axon pruning and could yield insight into neurodegenerative diseases involving aberrant axon pruning.