Axonal regeneration in adult CNS neurons--signaling molecules and pathways.
Failure of severed adult CNS axons to regenerate could be attributed to both a reduced intrinsic capacity to grow and an heightened susceptibility to inhibitory factors of the CNS extracellular environment. A particularly interesting and useful paradigm for investigating CNS axonal regeneration is its enhancement at the CNS branch of dorsal root ganglion (DRG) neurons after conditional lesioning of their peripheral branch. Recent reports have implicated the involvement of two well-known signaling pathways utilizing separate transcription factors; the Cyclic AMP (cAMP) response element binding protein (CREB) and signal transducer and activator of transcription 3 (STAT3), in conditional lesioning. The former appears to be the pathway activated by neurotrophic factors and Bcl-2, while the latter is responsible for the neurogenic effect of cytokines [such as the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) elevated at lesion sites]. Recent findings also augmented earlier notions that modulations of the activity of another class of cellular signaling intermediate, the conventional protein kinase C (PKC), could result in a contrasting growth response by CNS neurons to myelin-associated inhibitors. We discuss these signaling pathways and mechanisms, in conjunction with other recent reports of regeneration enhancement and also within the context of what is known about aiding regeneration of injured CNS axons.
Department of Biochemistry Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Felicia Yu Hsuan
FY
Teng
Bor Luen
BL
Tang
D000818:Animals; D002490:Central Nervous System / Q000293:injuries* / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D006131:Growth Inhibitors; D009414:Nerve Growth Factors; D050796:STAT3 Transcription Factor; D011493:Protein Kinase C