{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:03:34Z","timestamp":1774411414361,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T00:00:00Z","timestamp":1671840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call Regional Excellence (Research Activity in the Ionian University, for the study of protein folding in neurodegenerative diseases) (FOLDIT) MIS 5047144"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The X chromosome gene PLP1 encodes myelin proteolipid protein (PLP), the most prevalent protein in the myelin sheath surrounding the central nervous system. X-linked dysmyelinating disorders such as Pelizaeus\u2013Merzbacher disease (PMD) or spastic paraplegia type 2 (SPG2) are typically caused by point mutations in PLP1. Nevertheless, numerous case reports have shown individuals with PLP1 missense point mutations which also presented clinical symptoms and indications that were consistent with the diagnostic criteria of multiple sclerosis (MS), a disabling disease of the brain and spinal cord with no current cure. Computational structural biology methods were used to assess the impact of these mutations on the stability and flexibility of PLP structure in order to determine the role of PLP1 mutations in MS pathogenicity. The analysis showed that most of the variants can alter the functionality of the protein structure such as R137W variants which results in loss of helix and H140Y which alters the ordered protein interface. In silico genomic methods were also performed to predict the significance of these mutations associated with impairments in protein functionality and could suggest a better definition for therapeutic strategies and clinical application in MS patients.<\/jats:p>","DOI":"10.3390\/brainsci13010042","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:45:54Z","timestamp":1672116354000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Silico Structural Analysis Predicting the Pathogenicity of PLP1 Mutations in Multiple Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Antigoni","family":"Avramouli","sequence":"first","affiliation":[{"name":"Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University, 491 00 Corfu, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios G.","family":"Krokidis","sequence":"additional","affiliation":[{"name":"Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University, 491 00 Corfu, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Themis P.","family":"Exarchos","sequence":"additional","affiliation":[{"name":"Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University, 491 00 Corfu, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-7847","authenticated-orcid":false,"given":"Panagiotis","family":"Vlamos","sequence":"additional","affiliation":[{"name":"Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University, 491 00 Corfu, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a020529","DOI":"10.1101\/cshperspect.a020529","article-title":"Schwann cell myelination","volume":"7","author":"Salzer","year":"2015","journal-title":"Cold Spring Harb. 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