Diving into neurons: cellular and molecular mechanisms to unlock axon regeneration

In adult mammals, neurons of the central nervous system (CNS) fail to regenerate their axon after injury and to reconnect their target, hindering functional reconnection. To address this unmet need, my recent studies have explored several aspects. First, I showed that axon guidance is active not only during development but also in the mature brain after injury and is responsible for reconnection failure. Second, I showed that the intrinsic regrowth capacity of adult neurons relies on the translational regulation of specific mRNAs, highlighting translation as a dynamic layer of gene regulation involved in axon injury response and regeneration.

Interestingly, it is now established that translation is compartmentalized within neurons and occurs locally in the axon in a soma-autonomous manner. This local translation ensures a rapid and efficient renewal of proteins essential for neuronal circuit development and function. However, very little is known about the role and parameters of local translation in CNS repair, notably in the regrowth capacity of injured axons.

In the light of our recent findings, I will discuss our understanding of the mechanisms underlying the inability of adult CNS neurons to regenerate, as well as current strategies to promote axon regrowth and their limitations. I will also present the rationale for exploring local translation in injured axons as a potential key of their regrowth and of reconnection in the adult CNS.