The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury
Open accessAbstract
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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ADAMTS proteases cleave several PNN CSPGs, including aggrecan, brevican, neurocan, versican, and phosphacan.
“For instance, ADAMTSs are known to cleave multiple PNN components including the CSPGs aggrecan, brevican, neurocan, versican, and phosphacan (Fig. 2) (Porter et al., 2005; Tauchi et al., 2012).”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Tauchi et al., 2012
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- Authors
- Tauchi, R., Imagama, S., Natori, T., Ohgomori, T., Muramoto, A., Shinjo, R., Matsuyama, Y., Ishiguro, N., & Kadomatsu, K.
- Affiliations
- Nagoya University (JP)
- Hamamatsu University School of Medicine (JP)
- Corresponding author
- Kadomatsu, Kenji
- Venue
- Journal of Neuroinflammation
- Published
- 2012-03-15
- Volume
- 9
- Issue
- 1
- Pages
- 53-53
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3334708
- OpenAlex
- W2101430926
- Cited by
- 91
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 11 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 2
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Nagoya University Repository (NAGOYA Repository) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (20390092, 23110002, 18390099)
- Japan Society for the Promotion of Science (23790360)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- ADAMTS-4, chondroitin sulfate proteoglycans, chondroitinase ABC, spinal cord injury, functional recovery, proteoglycan core protein, brevican, neurocan, phosphacan, neurite outgrowth, axon regeneration, motor recovery, neuroplasticity, spinal cord contusion
- MeSH terms
- ADAMTS4 Protein, Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Cerebellum, Disease Models, Animal, Female, Gene Expression Regulation, Motor Activity, Neurons, Procollagen N-Endopeptidase, Psychomotor Performance, Spinal Cord Injuries, Neurites, Rats, Sprague-Dawley, Recovery of Function, Rats, ADAM Proteins, Versicans, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Neurocan, Brevican
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