Neuroregeneration

The absence of an effective cure for central nervous system (CNS) injuries and neurodegenerative diseases is an outstanding and costly deficiency in modern medicine. A fundamental barrier to recovering function is weak CNS axon regeneration, which is also strongly impeded by scarring at the injury site. One exciting discovery with profound neurotherapeutic implications is a robust regeneration by mammalian central axons following a “conditioning” lesion. Identifying critical components of lesion conditioning pathways would represent a key step toward successfully treating CNS injuries and multiple neurodegenerative diseases, improving the quality of life for many people. Unfortunately, lesion conditioning has been studied in vertebrates for over 30 years without a comprehensive understanding.

The nematode C. elegans is an exceptional model animal for biological study. A lesion conditioning model in C. elegans would enable high-throughput progress in the broad, systematic discovery of genes and mechanisms, allowing mammalian research to focus on confirming relevance in a smaller set of homologous items. 

The Neurolab described a novel type of axon regeneration in C. elegans that exhibits a lesion conditioning effect (Chung, et al. PNAS 2016). There are many genetic and phenotypic similarities with mammalian lesion-conditioned regeneration, indicating that they are mediated by conserved regeneration pathways and cellular mechanisms. Our form of regeneration is a novel model for mammalian lesion-conditioned regeneration, allowing us to leverage many of the worm’s advantages to rapidly study lesion conditioning.