{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:44:36Z","timestamp":1780393476319,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI18\/0049"],"award-info":[{"award-number":["PI18\/0049"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI21\/01085"],"award-info":[{"award-number":["PI21\/01085"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI20\/0448"],"award-info":[{"award-number":["PI20\/0448"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["2021-SGR-01492"],"award-info":[{"award-number":["2021-SGR-01492"]}]},{"name":"Autonomous Catalan Government","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}]},{"name":"Autonomous Catalan Government","award":["PI18\/0049"],"award-info":[{"award-number":["PI18\/0049"]}]},{"name":"Autonomous Catalan Government","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}]},{"name":"Autonomous Catalan Government","award":["PI21\/01085"],"award-info":[{"award-number":["PI21\/01085"]}]},{"name":"Autonomous Catalan Government","award":["PI20\/0448"],"award-info":[{"award-number":["PI20\/0448"]}]},{"name":"Autonomous Catalan Government","award":["2021-SGR-01492"],"award-info":[{"award-number":["2021-SGR-01492"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fragile X-associated tremor\/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in adult FMR1 premutation carriers. The neuropathological hallmark of FXTAS is an intranuclear inclusion in neurons and astrocytes. Nearly 200 different proteins have been identified in FXTAS inclusions, being the small ubiquitin-related modifier 2 (SUMO2), ubiquitin and p62 the most highly abundant. These proteins are components of the protein degradation machinery. This study aimed to characterize SUMO2\/3 expression levels and autophagy process in human postmortem brain samples and skin fibroblast cultures from FXTAS patients. Results revealed that FXTAS postmortem brain samples are positive for SUMO2\/3 conjugates and supported the idea that SUMO2\/3 accumulation is involved in inclusion formation. Insights from RNA-sequencing data indicated that SUMOylation processes are significantly upregulated in FXTAS samples. In addition, the analysis of the autophagy flux showed the accumulation of p62 protein levels and autophagosomes in skin fibroblasts from FXTAS patients. Similarly, gene set analysis evidenced a significant downregulation in gene ontology terms related to autophagy in FXTAS samples. Overall, this study provides new evidence supporting the role of SUMOylation and autophagic processes in the pathogenic mechanisms underlying FXTAS.<\/jats:p>","DOI":"10.3390\/cells12192364","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:04:18Z","timestamp":1695783858000},"page":"2364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploration of SUMO2\/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor\/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-8915","authenticated-orcid":false,"given":"Maria Isabel","family":"Alvarez-Mora","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Fundacio de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-9933","authenticated-orcid":false,"given":"Gl\u00f2ria","family":"Garrabou","sequence":"additional","affiliation":[{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Inherited Metabolic Diseases and Muscle Disorders\u2019 Research Laboratory (U722), Cellex-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Internal Medicine Department\u2013\u2013Hospital Cl\u00ednic Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8578","authenticated-orcid":false,"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[{"name":"Fundacio de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Neurological Tissue Bank of the Biobanc-Hospital Clinic-FCRB-IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Grillo-Risco","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Garcia-Garcia","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), 46012 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Barcos","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Cant\u00f3-Santos","sequence":"additional","affiliation":[{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Inherited Metabolic Diseases and Muscle Disorders\u2019 Research Laboratory (U722), Cellex-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Internal Medicine Department\u2013\u2013Hospital Cl\u00ednic Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-3929","authenticated-orcid":false,"given":"Laia","family":"Rodriguez-Revenga","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Fundacio de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/gm401","article-title":"FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States","volume":"4","author":"Tassone","year":"2012","journal-title":"Genome Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1086\/386296","article-title":"The fragile-X premutation: A maturing perspective","volume":"74","author":"Hagerman","year":"2004","journal-title":"Am. 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