Axonal regeneration and degeneration: cellular and molecular mechanisms (2016–2020)
The axon is the longest of a neuron¿s processes and it is essential for the formation and maintenance of a neuronal circuit. One of the most challenging and least understood phenomena in neuroscience is the characteristic and limited ability of mature adult neurons to regenerate and repair axonal damage. This has severely hampered the development of effective therapies to treat patients with peripheral and central nervous system injuiries, often resulting in permanent disabilities and poor clinical outcomes. Research in my laboratory has recently revealed the cellular and molecular elements regulating an alternative regenerative process, axonal fusion, observed in the nematode C. elegans and in several invertebrate species. In this case, following an axonal-severing injury, the two separated axonal fragments are able to rejoin and re-establish the original axonal tract, preventing degeneration of the distal axonal fragment. This process is mediated by specific transmembrane molecules called fusogens, and regulated by highly conserved elements of the apoptotic clearance machinery. Understanding in greater detail the molecular mechanisms of this biological event, will allow us to determine its translational potential as a novel therapeutic approach to treat neuronal injuries. The overall aim of my research is therefore to use the powerful genetic tools available for the nematode C. elegans to study key molecular elements and potential therapeutic targets to repair neuronal damage and prevent degeneration.