Actions of neurotrophic factors and their signaling pathways in neuronal surviva

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Mol Neurobiol. 2006 Apr;33(2):155-79.

Actions of neurotrophic factors and their signaling pathways in

neuronal survival and axonal regeneration.

Cui Q.

Laboratory for Neural Repair, Shantou University Medical College,

China.

Adult axons in the mammalian central nervous system do not elicit

spontaneous regeneration after injury, although many affected neurons

have survived the neurotrauma. However, axonal regeneration does

occur under certain conditions. These conditions include: (a)

modification of regrowth environment, such as supply of peripheral

nerve bridges and transplantation of Schwann cells or olfactory

ensheathing glia to the injury site; ( application of neurotrophic

factors at the cell soma and axon tips; © blockade of growth-

inhibitory molecules such as Nogo-A, myelin-associated glycoprotein,

and oligodendrocyte-myelin glycoprotein; (d) prevention of

chondroitin-sulfate-proteoglycans-related scar tissue formation at

the injury site using chondroitinase ABC; and (e) elevation of

intrinsic growth potential of injured neurons via increasing

intracellular cyclic adenosine monophosphate level.

A large body of evidence suggests that these conditions achieve

enhanced neuronal survival and axonal regeneration through sometimes

overlapping and sometimes distinct signal transduction mechanisms,

depending on the targeted neuronal populations and intervention

circumstances. This article reviews the available information on

signal transduction pathways underlying neurotrophic-factor-mediated

neuronal survival and neurite outgrowth/axonal regeneration.

Better understanding of signaling transduction is important in

helping us develop practical therapeutic approaches for encouraging

neuronal survival and axonal regeneration after traumatic injury in

clinical context.