Axonal Regeneration-related Molecules as Biomarkers for Multiple Sclerosis

Abstract

Abnormalities in both the nervous and immune systems are thought to be relevant to the pathogenesis of multiple sclerosis (MS). Several functional molecules closely related to axonal regeneration play an important role in not only the nervous system, but also the immune system. Many recent studies revealed that these molecules are associated with the neurological and immunological aspects of the pathogenesis of MS. Therefore, we focused on these molecules as promising biomarkers for MS. Nogo protein and its receptor (Nogo receptor-1; NgR1) are well known representative molecules that prevent axonal regeneration, and we identified lateral olfactory tract usher substance (LOTUS) as an endogenous antagonist of NgR1. We found that LOTUS expression was decreased in the spinal cord in an experimental autoimmune encephalomyelitis mouse model and that variations in LOTUS concentration in the cerebrospinal fluid correlated well with disease activity in MS patients. On the other hand, previous studies have shown that repulsive guidance molecule-a and semaphorins, known to be involved in axonal guidance and regeneration, play a role in MS pathogenesis. We review the association of these molecules with the neurological and immunological aspects of MS pathogenesis, and we show that they are promising, clinically-relevant biomarkers for MS.