Review articleHeparanase: Potential roles in multiple sclerosis

- The enzyme heparanase is ubiquitously expressed throughout the body, with pleiotrophic actions on various cell types
- Heparanase has roles in angiogenesis, cell signaling, tumor growth, inflammation, and regulation of the extracellular matrix
- Heparanase activities are implicated in stroke, Alzheimer's disease, and glioblastoma, suggesting similar roles in MS
- Methods to reduce heparanase expression or activity may be of value for treatment of MS

Heparanase is a heparan sulfate degrading enzyme that cleaves heparan sulfate (HS) chains present on HS proteoglycans (HSPGs), and has been well characterized for its roles in tumor metastasis and inflammation. However, heparanase is emerging as a contributing factor in the genesis and severity of a variety of neurodegenerative diseases and conditions. This is in part due to the wide variety of HSPGs on which the presence or absence of HS moieties dictates protein function. This includes growth factors, chemokines, cytokines, as well as components of the extracellular matrix (ECM) which in turn regulate leukocyte infiltration into the CNS. Roles for heparanase in stroke, Alzheimer's disease, and glioma growth have been described; roles for heparanase in other disease such as multiple sclerosis (MS) are less well established. However, given its known roles in inflammation and leukocyte infiltration, it is likely that heparanase also contributes to MS pathology. In this review, we will briefly summarize what is known about heparanase roles in the CNS, and speculate as to its potential role in regulating disease progression in MS and its animal model EAE (experimental autoimmune encephalitis), which may justify testing of heparanase inhibitors for MS treatment.