Does the expression of versican isoforms contribute to the pathogenesis of neurodegenerative diseases?

Abstract

Classical neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's are most commonly seen in older persons. The incidence rate increases as life expectancy increases. Even though neuronal loss, neuronal death and accumulated toxic proteins are well investigated, the mechanism(s) of neurodegenerative disorders is not yet fully understood. Versican is a large extracellular matrix proteoglycan. Its isoforms are aberrantly expressed in central nervous system injuries. Diverse lines of evidence suggest that versican isoforms play a vital role in regulating neuronal differentiation, maturation, neurite outgrowth, and synaptic transmission. Some toxic proteins may be increased and less sensitive to degeneration due to the chondroitin sulfate (CS) chains of versicans. We propose that the patterns of versican V1 and V2 isoforms act as a fine-tuned mechanism for guiding the change of neural microenvironment, and the unbalanced expression of V1 and V2 isoforms may contribute to the pathogenesis of neurodegenerative diseases. The emergence of versican isoforms indicates that it may explain the pathogenesis of the common sporadic forms of complex diseases.