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A sulfated disaccharide derived from chondroitin sulfate proteoglycan protects against inflammation‐associated neurodegeneration
Author(s) -
Rolls Asya,
Cahalon Liora,
Bakalash Sharon,
Avidan Hila,
Lider Ofer,
Schwartz Michal
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4540fje
Subject(s) - chondroitin sulfate proteoglycan , experimental autoimmune encephalomyelitis , inflammation , microglia , proteoglycan , neurodegeneration , chondroitin sulfate , immune system , chemistry , microbiology and biotechnology , tumor necrosis factor alpha , immunology , biology , biochemistry , medicine , glycosaminoglycan , extracellular matrix , disease
Chondroitin sulfate proteoglycan (CSPG), a matrix protein that occurs naturally in the central nervous system (CNS), is considered to be a major inhibitor of axonal regeneration and is known to participate in activation of the inflammatory response. The degradation of CSPG by a specific enzyme, chondroitinase ABC, promotes repair. We postulated that a disaccharidic degradation product of this glycoprotein (CSPG‐DS), generated following such degradation, participates in the modulation of the inflammatory responses and can, therefore, promote recovery in immune‐induced neuropathologies of the CNS, such as experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune uveitis (EAU). In these pathologies, the dramatic increase in T cells infiltrating the CNS is far in excess of the numbers needed for regular maintenance. Here, we show that CSPG‐DS markedly alleviated the clinical symptoms of EAE and protected against the neuronal loss in EAU. The last effect was associated with a reduction in the numbers of infiltrating T cells and marked microglia activation. This is further supported by our in vitro results indicating that CSPG‐DS attenuated T cell motility and decreased secretion of the cytokines interferon‐? and tumor necrosis factor‐?. Mechanistically, these effects are associated with an increase in SOCS‐3 levels and a decrease in NF‐?B. Our results point to a potential therapeutic modality, in which a compound derived from an endogenous CNS‐resident molecule, known for its destructive role in CNS recovery, might be helpful in overcoming inflammation‐induced neurodegenerative conditions.