{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:35:39Z","timestamp":1790134539689,"version":"4.0.1"},"reference-count":97,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A.A.S. is a recipient of a predoctoral fellowship from the Basque Government","award":["(PRE_2017_1_0016)"],"award-info":[{"award-number":["(PRE_2017_1_0016)"]}]},{"name":"M.L.M. is a recipient of a fellowship from Foundation \u201cJes\u00fas de Gangoiti y Barrera\u201d.","award":["Jes\u00fas de Gangoiti y Barrera 2019"],"award-info":[{"award-number":["Jes\u00fas de Gangoiti y Barrera 2019"]}]},{"name":"J.L.Z. was supported by the Instituto de Salud Carlos III","award":["(PI18\/00207)"],"award-info":[{"award-number":["(PI18\/00207)"]}]},{"name":"J.L.Z. was supported by  University of Basque Country Grant.","award":["(US19\/04)"],"award-info":[{"award-number":["(US19\/04)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>McArdle disease, also known as glycogen storage disease type V (GSDV), is characterized by exercise intolerance, the second wind phenomenon, and high serum creatine kinase activity. Here, we recapitulate PYGM mutations in the population responsible for this disease. Traditionally, McArdle disease has been considered a metabolic myopathy caused by the lack of expression of the muscle isoform of the glycogen phosphorylase (PYGM). However, recent findings challenge this view, since it has been shown that PYGM is present in other tissues than the skeletal muscle. We review the latest studies about the molecular mechanism involved in glycogen phosphorylase activity regulation. Further, we summarize the expression and functional significance of PYGM in other tissues than skeletal muscle both in health and McArdle disease. Furthermore, we examine the different animal models that have served as the knowledge base for better understanding of McArdle disease. Finally, we give an overview of the latest state-of-the-art clinical trials currently being carried out and present an updated view of the current therapies.<\/jats:p>","DOI":"10.3390\/ijms20235919","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T11:12:21Z","timestamp":1574680341000},"page":"5919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["McArdle Disease: New Insights into Its Underlying Molecular Mechanisms"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-8004","authenticated-orcid":false,"given":"Francisco","family":"Llavero","sequence":"first","affiliation":[{"name":"Achucarro Basque Center for Neuroscience, Science Park of the Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Faculty of Sports Science, European University of Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alazne","family":"Arrazola Sastre","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience, Science Park of the Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Department of Genetics, Physical Anthropology, and Animal Physiology, Faculty of Science and Technology, UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Luque Montoro","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience, Science Park of the Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"G\u00e1lvez","sequence":"additional","affiliation":[{"name":"Pharmascience Division, Technological Park of Health Sciences, Avda. de la Ciencia, s\/n 18100 Armilla, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadriano M","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Three R Labs, Science Park of the UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Parada","sequence":"additional","affiliation":[{"name":"Instituto de Patolog\u00eda Experimental, Universidad Nacional de Salta, 4400 Salta, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Zugaza","sequence":"additional","affiliation":[{"name":"Achucarro Basque Center for Neuroscience, Science Park of the Universidad del Pa\u00eds Vasco\/Euskal Herriko Unibertsitatea (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Department of Genetics, Physical Anthropology, and Animal Physiology, Faculty of Science and Technology, UPV\/EHU, 48940 Leioa, Spain"},{"name":"IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/BF00205166","article-title":"Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence","volume":"86","author":"Lebo","year":"1990","journal-title":"Hum. 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