Proteoglycans and neurological diseases

Abstract

Proteoglycans (PGs) consist of a core protein and glycosaminoglycans (GAGs). They are components of the extracellular matrices of the central nervous system (CNS) and also are present in the peripheral nervous system. They have been reported to be axon regenerating inhibitors in the CNS. They may therefore affect the pathogenetic mechanisms of the neurological diseases, but their roles have rarely been studied so far. Recently we investigated experimental autoimmune encephalomyelitis (EAE) induced in the mice deficient in glycosyltransferases involved in the synthesis of GAGs and found that modification of the carbohydrate residue of PGs have major effects on the pathogenesis of EAE. About half of the patients with IgM paraproteinemic neuropathy (IgM–N), IgM M–proteins are known to recognize HNK–1 epitope of myelin–associated glycoprotein (MAG). Phosphacan is a proteoglycan, which also has HNK–1 epitope. We studied binding specificities of such IgM M–proteins and found that they were heterogeneous. The ratio of the binding activity to phosphacan divided by that to MAG (P/M ratio) was related with the clinical severity of IgM–N. Further investigation on the roles of PGs in the neurological diseases may lead to the understanding of the pathogenesis and the development of novel therapies of neurological diseases.