Some hypotheses concerning axon regeneration

We review evidence related to several hypotheses concerning the mechanism of axon regeneration and present new data addressing one hypothesis. That one hypothesis concerns the signal that initiates changes in the cell bodies of neurons after axon damage. We identify a molecule that has a number of the properties expected of such a signal. We also review the hypothesis that induction of some genes is tightly correlated with nerve regeneration, and conclude that such a correlation is not so 'tight'. Nevertheless, proteins whose rate of synthesis or transport is increased in some systems are good candidates for playing important roles in regrowth. A third hypothesis, that mammalian CNS neurons fail to regenerate because of a failure to induce growth-associated proteins, is probably not true. Growth-associated proteins appear to be induced, at least transiently, in some cases where regeneration is abortive. The state of the neuron undoubtedly is important in regeneration, but many neurons, even in the CNS, appear to be able to support axon regrowth given the proper environment. Thus, support seems stronger for the view that the environment at the site of damage (including surfaces and growth factors) determines whether significant regrowth occurs in most cases.