Abstract
Spinal cord injury is a debilitating condition that affects over 200 people annually in New Zealand. Injury pathophysiology is caused by damage to axons in the spinal cord, which are protrusions that extend from neurons and facilitate the transmission of motor and sensory information. Axons are unable to regrow, and so paralysis and a loss of sensation often occur below the site of injury. These symptoms have no cure, and so research continues to explore systems that limit axonal regeneration, including intrinsic growth capacities of neurons and the inhibitory environment that is formed at the lesion.
Recent work has shown that Microtubule Associated Protein 2 (MAP2) regulates the transport of proteins and cargo, such as cellular organelles, into axons. Encouragingly, the removal of MAP2 enhances axon outgrowth, even in inhibitory environments. L1 Cell Adhesion Molecule (L1CAM) emerged as a protein of interest potentially linked to MAP2 activity and is a mediator of neuronal adhesion and neural growth processes such as migration, axon guidance and neurite extension.
This research aimed to investigate the role of L1CAM in axonal regeneration. It was hypothesised that the increased regeneration following MAP2 depletion results from the downstream effects on L1CAM. A functional association between these proteins was demonstrated by reduced L1CAM expression and localisation upon MAP2 depletion, as well as an increase in MAP2 protein levels in the cell body and axon when L1CAM was reduced. Additionally, a short hairpin RNA construct was developed to silence L1CAM and investigate direct effects on axon outgrowth. Notably, although silencing L1CAM did not significantly affect axon outgrowth, it appeared to diminish the negative impact of a restrictive environment.
Together these findings reveal a reciprocal relationship between MAP2 and L1CAM localisation and suggest that L1CAM knockdown may help mitigate the impact of growth-inhibitory environments, rather than directly enhancing axonal growth. This points toward a potential mechanism underlying the increased regeneration observed in MAP2–depleted neurons within inhibitory contexts.