Bolino, AlessandraPiguet, FrançoiseAlberizzi, ValeriaPellegatta, MartaRivellini, CristinaNoseda, RobertaBrombin, ChiaraNonis, AlessandroD'Adamo, PatriziaTaveggia, CarlaPrevitali, Stefano C.Guerrero Valero, Marta2026-02-252026-02-252016Bolino A, Piguet F, Alberizzi V, et al. Niacin‐mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination. EMBO Mol Med 2016;8:1438–54. https://doi.org/10.15252/emmm.20160634910.15252/emmm.201606349https://hdl.handle.net/20.500.14352/133160Charcot-Marie-Tooth (CMT) neuropathies are highly heterogeneous disorders caused by mutations in more than 70 genes, with no available treatment. Thus, it is difficult to envisage a single suitable treatment for all pathogenetic mechanisms. Axonal Neuregulin 1 (Nrg1) type III drives Schwann cell myelination and determines myelin thickness by ErbB2/B3-PI3K-Akt signaling pathway activation. Nrg1 type III is inhibited by the α-secretase Tace, which negatively regulates PNS myelination. We hypothesized that modulation of Nrg1 levels and/or secretase activity may constitute a unifying treatment strategy for CMT neuropathies with focal hypermyelination as it could restore normal levels of myelination. Here we show that in vivo delivery of Niaspan, a FDA-approved drug known to enhance TACE activity, efficiently rescues myelination in the Mtmr2-/- mouse, a model of CMT4B1 with myelin outfoldings, and in the Pmp22+/- mouse, which reproduces HNPP (hereditary neuropathy with liability to pressure palsies) with tomacula. Importantly, we also found that Niaspan reduces hypermyelination of Vim (vimentin)-/- mice, characterized by increased Nrg1 type III and Akt activation, thus corroborating the hypothesis that Niaspan treatment downregulates Nrg1 type III signaling.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.15252/emmm.201606349http://europepmc.org/abstract/med/27799291open access577.2612.8Animal modelsCharcot–Marie–Tooth neuropathiesMyelinNeuregulin 1Nicotinic acidBiología molecular (Farmacia)Neurociencias (Farmacia)2415 Biología Molecular