Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.

A nanopatterned interdigitated electrode array (nanoIEA)‐based impedance assay is developed for quantitative real‐time measurement of aligned endothelial cell (EC) barrier functions in vitro. A bioinspired poly(3,4‐dihydroxy‐L‐phenylalanine) (poly (l‐DOPA)) coating is applied to improve the human brain EC adhesion onto the Nafion nanopatterned surfaces. It is found that a poly (l‐DOPA)‐coated Nafion grooved nanopattern makes the human brain ECs orient along the nanopattern direction. Aligned human brain ECs on Nafion nanopatterns exhibit increased expression of genes encoding tight and adherens junction proteins. Aligned human brain ECs also have enhanced impedance and resistance versus unaligned ones. Treatment with a glycogen synthase kinase‐3 inhibitor (GSK3i) further increases impedance and resistance, suggesting synergistic effects occur on the cell–cell tightness of in vitro human brain ECs via a combination of anisotropic matrix nanotopography and GSK3i treatment. It is found that this enhanced cell–cell tightness of the combined approach is accompanied by increased expression of claudin protein. These data demonstrate that the proposed nanoIEA assay integrated with poly (l‐DOPA)‐coated Nafion nanopatterns and interdigitated electrode arrays can make not only biomimetic aligned ECs, but also enable real‐time measurement of the enhanced barrier functions of aligned ECs via tighter cell–cell junctions.

Cheong C, et al. Ann Surg Treat Res. 2025 Nov;109(5):335-343. https://doi.org/10.4174/astr.2025.109.5.335