Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration

Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulati...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2015-06, Vol.8, p.26-26
Main Authors: Siddiq, Mustafa M, Hannila, Sari S
Format: Article
Language:English
Subjects:
Arginase
CREB
Cyclic AMP
Cyclic AMP response element-binding protein
Cytokines
Dorsal root ganglia
gene
Gene expression
Glycoproteins
Interleukin 6
Kinases
Metallothionein
Myelin
Myelin-associated glycoprotein
Nervous system
Neurodegeneration
Neurons
Neuroscience
Nogo protein
Oligodendrocyte-myelin glycoprotein
Polyamines
Protein kinase A
Proteinase inhibitors
Proteins
Regeneration
RNA polymerase
Roles
Rolipram
Spinal cord injuries
Transcription factors
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Summary:Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulation of cAMP through the administration of dibutyryl cAMP or rolipram leads to enhanced axonal growth both in vivo and in vitro, and importantly, upregulation of cAMP within dorsal root ganglion neurons is responsible for the conditioning lesion effect, which indicates that cAMP plays a significant role in the endogenous mechanisms that promote axonal regeneration. The effects of cAMP are transcription-dependent and are mediated through the activation of protein kinase A (PKA) and the transcription factor cyclic AMP response element binding protein (CREB). This leads to the induction of a variety of genes, several of which have been shown to overcome myelin-mediated inhibition in their own right. In this review, we will highlight the pro-regenerative effects of arginase I (ArgI), interleukin (IL)-6, secretory leukocyte protease inhibitor (SLPI), and metallothionein (MT)-I/II, and discuss their potential for therapeutic use in spinal cord injury.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2015.00026