{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:46:51Z","timestamp":1753876011211,"version":"3.41.2"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["#MDA 957250","#GGP20063"],"award-info":[{"award-number":["#MDA 957250","#GGP20063"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Joint Programme on Rare Diseases","award":["ERP-2019-23680644"],"award-info":[{"award-number":["ERP-2019-23680644"]}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD105353"],"award-info":[{"award-number":["P50 HD105353"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Charcot-Marie-Tooth (CMT) neuropathies represent a broad and very heterogeneous group of disorders for which no therapies are yet available. Due to the huge genetic heterogeneity, therapeutical approaches that can benefit several forms independently of the unique pathogenetic mechanism have been sought. Niacin, nicotinic acid, is a vitamin used for many decades as anti-dyslipidaemic and anti-cholesterol drug product under the commercial name of Niaspan\u00ae, the extended-release formulation of niacin. Of note, niacin can have other effects depending on the dose, formulation and physiology and it has been used to reduce inflammation, to promote angiogenesis and to protect neurons, muscle and axons by boosting nicotinamide adenine dinucleotide (NAD+) levels. Niacin also activates TNF-alpha convertase enzyme (TACE) secretase, which negatively regulates Neuregulin type I-mediated signalling in the peripheral nervous system and myelination. We previously postulated that niacin-mediated TACE activation can be effective in reducing aberrant excessive myelin associated with different CMT forms. Here, we explored efficacy of this strategy by performing a long-term preclinical trial and we provided evidence that a novel niacin-based long-lasting formulation ameliorates neurophysiology and reduces fibre degeneration in a model of Charcot-Marie-Tooth type 4B1 (CMT4B1) neuropathy, characterized by aberrant myelin. We also sought to determine whether this strategy might interfere with nerve regeneration, which is dependent on Neuregulin type I signalling. Surprisingly, we found that the Mtmr2 knockout mice, a model of CMT4B1, have a defect in nerve regeneration and that niacin-based treatment is not detrimental to nerve regeneration.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf039","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T17:42:06Z","timestamp":1738345326000},"source":"Crossref","is-referenced-by-count":0,"title":["Niacin ameliorates Charcot-Marie-Tooth 4B1 neuropathy without interfering with nerve regeneration"],"prefix":"10.1093","volume":"7","author":[{"given":"Silvia","family":"Cipriani","sequence":"first","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Human Inherited Neuropathies Unit , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0490-1538","authenticated-orcid":false,"given":"Emanuela","family":"Porrello","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Neuromuscular Repair Unit , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Cerea","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universit\u00e0 degli Studi di Milano , Milan 20133 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Gazzaniga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Universit\u00e0 degli Studi di Milano , Milan 20133 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Di Guardo","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Human Inherited Neuropathies Unit , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UKDRI Fluid Biomarker Laboratory , London WC1N3BG ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Valenzano","sequence":"additional","affiliation":[{"name":"Department of Neurology, IRCCS Ospedale San Raffaele , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ubaldo","family":"Del Carro","sequence":"additional","affiliation":[{"name":"Department of Neurology, IRCCS Ospedale San Raffaele , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phu","family":"Duong","sequence":"additional","affiliation":[{"name":"Waisman Center and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-7921","authenticated-orcid":false,"given":"John","family":"Svaren","sequence":"additional","affiliation":[{"name":"Waisman Center and Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2546-4357","authenticated-orcid":false,"given":"Stefano Carlo","family":"Previtali","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Neuromuscular Repair Unit , Milan 20132 ,","place":["Italy"]},{"name":"Department of Neurology, IRCCS Ospedale San Raffaele , Milan 20132 ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele University , Milan 20132 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-4878","authenticated-orcid":false,"given":"Alessandra","family":"Bolino","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele, Human Inherited Neuropathies Unit , Milan 20132 ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele 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