ADAMTS proteoglycanases in the physiological and pathological central nervous system

Abstract

ADAMTS-1, -4, -5 and -9 belong to 'a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)' family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries.

Figure 1

Roles of ADAMTS proteoglycanases in the physiological and pathological central nervous system. Schematic representation of described (filled lines)/hypothetical (dotted lines) roles of ADAMTS proteoglycanases in the physiological (green) and pathological (red) CNS, with corresponding major references listed below. This schema also illustrates that ADAMTS proteoglycanases can achieve several functions in the physiological and pathological CNS via the cleavage of their substrates, so far CSPGs or Reelin, but also independently of their proteolytic activity. ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; CNS, central nervous system; CSPGs, chondroitin sulfate proteoglycans.