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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

Authors: Ryoji Tauchi, Shiro Imagama, Takamitsu Natori, Tomohiro Ohgomori, Akio Muramoto, Ryuichi Shinjo, Yukihiro Matsuyama, Naoki Ishiguro, Kenji Kadomatsu

Published in: Journal of Neuroinflammation | Issue 1/2012

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Abstract

Background

Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.

Methods

The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed.

Results

ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.

Conclusions

Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.
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Metadata
Title
The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury
Authors
Ryoji Tauchi
Shiro Imagama
Takamitsu Natori
Tomohiro Ohgomori
Akio Muramoto
Ryuichi Shinjo
Yukihiro Matsuyama
Naoki Ishiguro
Kenji Kadomatsu
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-53

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