Wallerian Degeneration Involves Rho/Rho-kinase Signaling

Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed “Wallerian degeneration,” as a model to examine the possible involvement o...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-05, Vol.280 (21), p.20384-20388
Main Authors: Yamagishi, Satoru, Fujitani, Masashi, Hata, Katsuhiko, Kitajo, Keiko, Mimura, Fumiaki, Abe, Hideki, Yamashita, Toshihide
Format: Article
Language:English
Subjects:
Amides - pharmacology
Animals
Axons - enzymology
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Female
Intracellular Signaling Peptides and Proteins
Myelin Proteins - pharmacology
Myelin Proteins - physiology
Myelin-Associated Glycoprotein - physiology
Myelin-Oligodendrocyte Glycoprotein
Nogo Proteins
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - metabolism
Pyridines - pharmacology
Rats
Rats, Wistar
rho GTP-Binding Proteins - metabolism
rho-Associated Kinases
Signal Transduction
Spinal Cord Injuries
Wallerian Degeneration - metabolism
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Summary:Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed “Wallerian degeneration,” as a model to examine the possible involvement of Rho. Nogo-66, a myelin-derived inhibitor of axon regeneration, significantly accelerated axon degeneration of the dorsal root ganglion explant in vitro, whereas inhibiting Rho-kinase activity abolished the effect. Rho activation was observed in the distal part of the injured axons after spinal cord injury. We demonstrate that degeneration of the injured cortico-spinal axons was significantly retarded by a Rho-kinase inhibitor in vivo. Our findings suggest that inhibiting the signaling pathway may retard axon degeneration in pathological conditions.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M501945200