Signaling regulations of neuronal regenerative ability

Abstract

Different from physiological axon growth during development, a major limiting factor for successful axon regeneration is the poor intrinsic regenerative capacity in mature neurons in the adult mammalian central nervous system (CNS). Recent studies identified several molecular pathways, including PTEN/mTOR, Jak/STAT, DLK/JNK, providing important probes in investigating the mechanisms by which the regenerative ability is regulated. This review will summarize these recent findings and speculate their implications.

Figure 1. A working model of the mechanisms that regulate the intrinsic regenerative ability of axon regeneration

(1) To respond to axotomy, the neuronal cell bodies need to be informed by retrogradely transported injury signals. In addition to acute axotomy-induced changes such as ion influx, cytokines such as IL-6 and CNTF are up-regulated at the lesion site and/or around the cell body. As a result, DLK and Jak/STAT pathways are activated, resulting in the generation and transport of the injury signals. (2). How injured neurons respond to injury signals is dependent on their regenerative competence. An important determinant of the competence might be the mTOR activity but other molecular pathways likely exist.