Search

Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot–Marie–Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r = − 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology. [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT neuropathy score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity. [ABSTRACT FROM AUTHOR]

Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human. [ABSTRACT FROM AUTHOR]