Loss of YAP in Schwann cells improves HNPP pathophysiology.

Autor: Moore SM; Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.; Institute for Myelin and Glia Exploration, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA., Jeong E; Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.; Institute for Myelin and Glia Exploration, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA., Zahid M; Institute for Myelin and Glia Exploration, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.; Department of Biological Sciences, University at Buffalo, Buffalo, New York, USA., Gawron J; Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.; Institute for Myelin and Glia Exploration, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA., Arora S; Albany Medical College, Department of Neuroscience and Experimental Therapeutics, Albany, New York, USA., Belin S; Albany Medical College, Department of Neuroscience and Experimental Therapeutics, Albany, New York, USA., Sim F; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA., Poitelon Y; Albany Medical College, Department of Neuroscience and Experimental Therapeutics, Albany, New York, USA., Feltri ML; Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.; Institute for Myelin and Glia Exploration, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.; Department of Neurology, University at Buffalo, Buffalo, New York, USA.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Nov; Vol. 72 (11), pp. 1974-1984. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1002/glia.24592
Abstrakt: 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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