Year: 2024
Type: article
Abstract: Rapid nerve conduction in the peripheral nervous system (PNS) is facilitated by the multilamellar myelin sheath encasing many axons of peripheral nerves. Charcot-Marie-Tooth type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsy (HNPP) are common demyelinating inherited peripheral neuropathies and are caused by mutations in the peripheral myelin protein 22 (PMP22) gene. Duplication of PMP22 leads to its overexpression and causes CMT1A, while its deletion results in PMP22 under expression and causes HNPP. Here, we investigated novel targets for modulating the protein level of PMP22 in HNPP. We found that genetic attenuation of the transcriptional coactivator Yap in Schwann cells reduces p-TAZ levels, increased TAZ activity, and increases PMP22 in peripheral nerves. Based on these findings, we ablated Yap alleles in Schwann cells of the Pmp22-haploinsufficient mouse model of HNPP and identified fewer tomacula on morphological assessment and improved nerve conduction in peripheral nerves. These findings suggest YAP modulation may be a new avenue for treatment of HNPP.
Source: Glia
DOI: 10.1002/glia.24592
Authors: Seth M. Moore, Eunbi Jeong, Muhammad Zahid, Joseph Gawron, Simar Arora, Sophie Belin, Fraser Sim, Yannick Poitelon, M. Laura Feltri
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: G1435893953, Laminin Receptors and Signals in Schwann Cells, G3309632404, G3668981610, G6341943917, YAP/TAZ in Schwann Cells as Potential Therapeutic Targets in CMT1A and HNPP., Transduction of Mechanical Stimuli in Myelination and Peripheral Nerve Repair, Role of a Fatty Acid Chaperone in Schwann Cell Myelination
OpenAlex ID: W4400552913