Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System
Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System
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DOI：
10.1002/9783527610365.ch2
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发表时间：
2007-02
期刊：
影响因子：
--
通讯作者：
F. Rossi
中科院分区：
文献类型：
--
作者：
F. Rossi
Introduction The success or failure of neural circuit rewiring through axon regeneration depends on the interplay between two main determinants. The injured neurons must synthesize structural components for outgrowing processes and activate signal transduction pathways to sense and decode guidance cues. At the same time, the surrounding microenvironment must provide suitable substrates and information to promote and direct axon elongation. Although there is general agreement that both neuronal and environmental factors are responsible for the poor outcome of brain repair, over the past decades attention has been mainly focused on the latter aspect. In particular, the observation that adult central nervous system (CNS) neurites can elongate into the growth-permissive peripheral nervous system (PNS) environment (Bray and Aguayo, 1989), together with the discovery that myeli-nating oligodendrocytes express neurite growth-inhibitory proteins (Schwab et al., 1993), have led to the notion that central neurons may be capable of regrowing their axons, but they fail because of adverse environmental conditions. Accordingly, in recent years an expanding set of growth-inhibitory molecules and related signal-ing pathways have been described in the CNS milieu (e. observations indicate that the intrinsic properties of the affected neurons are also crucial to determine the result of repair processes. Different types of nerve cells, when confronted with the same environment, show remarkably variable regenerative capabilities, from growth cone formation The strength of regenerative phenomena is tightly related to the activity of a set of neuronal genes associated with growth cone function and process elongation (Fawcett, 2001; Fawcett et al., 2001; Fernandes and Tetzlaff, 2001). The ability for up-regulating such genes in response to injury is not equal among central neurons (Herdegen et al. As a consequence, the neutralization of major inhibitory cues may result scarcely effective, if not accompanied by the activation of intrinsic neuritic growth mechanisms (Fischer et al., 2004a,b). These observations indicate that removal of extrinsic inhibition may be important , but it is not sufficient to achieve CNS repair. On the other hand, it is also clear that in adult neurons the molecular machinery required to sustain neuritic growth is not constitutively active, but it is subject to strict control mechanisms, the nature and biological meaning of which are still unclear. In this chapter, current knowledge about the role of intrinsic factors in axon regeneration will be reviewed, and the main mechanisms that regulate their expression and function described. Finally, the physiological significance of neuritic growth control in …
