title: The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury.
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.
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tauchi
authors.forename: Shiro
authors.initials: S
authors.lastname: Imagama
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Natori
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ohgomori
authors.forename: Akio
authors.initials: A
authors.lastname: Muramoto
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shinjo
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsuyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism / Q000627:therapeutic use*; D000071121:ADAMTS4 Protein; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D058581:Brevican / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D058580:Neurocan / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000378:metabolism / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D053675:Versicans / Q000378:metabolism
chemical_list: D058581:Brevican; D058580:Neurocan; C508324:Vcan protein, rat; D053675:Versicans; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein