Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in adult <i>FMR1</i> premutation carriers. The neuropathological hallmark of FXTAS is an intranuclear inclusion in neurons and astrocytes. Nearly 200 different proteins have been i...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/19/2364 |
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| author | Maria Isabel Alvarez-Mora Glòria Garrabou Laura Molina-Porcel Ruben Grillo-Risco Francisco Garcia-Garcia Tamara Barcos Judith Cantó-Santos Laia Rodriguez-Revenga |
| author_facet | Maria Isabel Alvarez-Mora Glòria Garrabou Laura Molina-Porcel Ruben Grillo-Risco Francisco Garcia-Garcia Tamara Barcos Judith Cantó-Santos Laia Rodriguez-Revenga |
| author_sort | Maria Isabel Alvarez-Mora |
| collection | DOAJ |
| description | Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in adult <i>FMR1</i> 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 <i>postmortem</i> brain samples and skin fibroblast cultures from FXTAS patients. Results revealed that FXTAS <i>postmortem</i> 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. |
| first_indexed | 2024-03-10T21:47:30Z |
| format | Article |
| id | doaj.art-4ee105238e33440e9811ba0e0c9374d5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:47:30Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4ee105238e33440e9811ba0e0c9374d52023-11-19T14:12:45ZengMDPI AGCells2073-44092023-09-011219236410.3390/cells12192364Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future ResearchMaria Isabel Alvarez-Mora0Glòria Garrabou1Laura Molina-Porcel2Ruben Grillo-Risco3Francisco Garcia-Garcia4Tamara Barcos5Judith Cantó-Santos6Laia Rodriguez-Revenga7Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, SpainCIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, SpainFundacio de Recerca Clínic Barcelona-Institut d’Investigacions Biomediques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, SpainBioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), 46012 Valencia, SpainBioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), 46012 Valencia, SpainBiochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, SpainCIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, SpainBiochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, SpainFragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in adult <i>FMR1</i> 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 <i>postmortem</i> brain samples and skin fibroblast cultures from FXTAS patients. Results revealed that FXTAS <i>postmortem</i> 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.https://www.mdpi.com/2073-4409/12/19/2364<i>FMR1</i> premutationFXTASSUMO2/3p62SUMOylationautophagy |
| spellingShingle | Maria Isabel Alvarez-Mora Glòria Garrabou Laura Molina-Porcel Ruben Grillo-Risco Francisco Garcia-Garcia Tamara Barcos Judith Cantó-Santos Laia Rodriguez-Revenga Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research Cells <i>FMR1</i> premutation FXTAS SUMO2/3 p62 SUMOylation autophagy |
| 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 |
| title_full | Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research |
| title_fullStr | Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research |
| title_full_unstemmed | Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research |
| title_short | Exploration of SUMO2/3 Expression Levels and Autophagy Process in Fragile X-Associated Tremor/Ataxia Syndrome: Addressing Study Limitations and Insights for Future Research |
| title_sort | exploration of sumo2 3 expression levels and autophagy process in fragile x associated tremor ataxia syndrome addressing study limitations and insights for future research |
| topic | <i>FMR1</i> premutation FXTAS SUMO2/3 p62 SUMOylation autophagy |
| url | https://www.mdpi.com/2073-4409/12/19/2364 |
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