p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies

Abstract

Objective Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease‐relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results Enzyme‐linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype‐specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation This study indicates that the identification of disease‐specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

“…Using the myelination and demyelination markers, MPZ and NCAM, respectively, we measured the myelination by Schwann cells at the sciatic nerve. Previously, it was reported that the expression level of NCMA correlated with demyelination status in the CMT1A mouse model [40]. Double staining with MPZ and NCAM antibodies revealed that control-diet-fed C22 mice had higher levels of NCAM and lower levels of MPZ compared to wild-type mice (Figure 5A).…”

Behind the pathology of macrophage-associated demyelination in inflammatory neuropathies: demyelinating Schwann cells

“…Several biochemical features of DSCs in WD (wDSCs), such as the expression of c-jun and p75, together with shutdown of the expression of myelin genes and an increase in autolysosomes were also observed in the SC of the animal models of inflammatory demyelinating neuropathy, in which the axon is relatively intact [1,10,12]. Previous results and our recent study demonstrated the presence of potential DSCs in human inflammatory demyelinating nerves using biopsy specimens and patient sera, respectively [15,16], which suggests a pathological implication of DSCs in demyelinating neuropathies. However, the contribution of the demyelinating ability of DSCs, which may be inevitably accompanied by these inflammatory attack factors, on the pathogenesis of inflammatory demyelination has not been significantly considered in the clinical field.…”

Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies

“…Further blood biomarkers are currently investigated using proteomics approaches. Significant serum elevation of neural cell adhesion molecule-1 (NCAM1) was shown in CMT1A patients as well as in patients with various forms of inflammatory neuropathies [ 228 ]. This biomarker was also elevated in a mouse model of CMT1X and showed responsiveness to GJB1 gene replacement therapy [ 34 ].…”