Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity
α-Synuclein inclusion bodies are a pathological hallmark of several neurodegenerative diseases, including Parkinson’s disease, and contain aggregated α-synuclein and a variety of recruited factors, including protein chaperones, proteasome components, ubiquitin and the small ubiquitin-like modifier,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-07-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/5/3/1697 |
| _version_ | 1818494206807638016 |
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| author | Shamini Vijayakumaran Mathew B. Wong Helma Antony Dean L. Pountney |
| author_facet | Shamini Vijayakumaran Mathew B. Wong Helma Antony Dean L. Pountney |
| author_sort | Shamini Vijayakumaran |
| collection | DOAJ |
| description | α-Synuclein inclusion bodies are a pathological hallmark of several neurodegenerative diseases, including Parkinson’s disease, and contain aggregated α-synuclein and a variety of recruited factors, including protein chaperones, proteasome components, ubiquitin and the small ubiquitin-like modifier, SUMO-1. Cell culture and animal model studies suggest that misfolded, aggregated α-synuclein is actively translocated via the cytoskeletal system to a region of the cell where other factors that help to lessen the toxic effects can also be recruited. SUMO-1 covalently conjugates to various intracellular target proteins in a way analogous to ubiquitination to alter cellular distribution, function and metabolism and also plays an important role in a growing list of cellular pathways, including exosome secretion and apoptosis. Furthermore, SUMO-1 modified proteins have recently been linked to cell stress responses, such as oxidative stress response and heat shock response, with increased SUMOylation being neuroprotective in some cases. Several recent studies have linked SUMOylation to the ubiquitin-proteasome system, while other evidence implicates the lysosomal pathway. Other reports depict a direct mechanism whereby sumoylation reduced the aggregation tendency of α-synuclein, and reduced the toxicity. However, the precise role of SUMO-1 in neurodegeneration remains unclear. In this review, we explore the potential direct or indirect role(s) of SUMO-1 in the cellular response to misfolded α-synuclein in neurodegenerative disorders. |
| first_indexed | 2024-12-10T18:03:32Z |
| format | Article |
| id | doaj.art-e266264ef1ff4cf795f192baa1a09e11 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-10T18:03:32Z |
| publishDate | 2015-07-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj.art-e266264ef1ff4cf795f192baa1a09e112022-12-22T01:38:42ZengMDPI AGBiomolecules2218-273X2015-07-01531697171610.3390/biom5031697biom5031697Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein ToxicityShamini Vijayakumaran0Mathew B. Wong1Helma Antony2Dean L. Pountney3Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, AustraliaMenzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, AustraliaMenzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, AustraliaMenzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australiaα-Synuclein inclusion bodies are a pathological hallmark of several neurodegenerative diseases, including Parkinson’s disease, and contain aggregated α-synuclein and a variety of recruited factors, including protein chaperones, proteasome components, ubiquitin and the small ubiquitin-like modifier, SUMO-1. Cell culture and animal model studies suggest that misfolded, aggregated α-synuclein is actively translocated via the cytoskeletal system to a region of the cell where other factors that help to lessen the toxic effects can also be recruited. SUMO-1 covalently conjugates to various intracellular target proteins in a way analogous to ubiquitination to alter cellular distribution, function and metabolism and also plays an important role in a growing list of cellular pathways, including exosome secretion and apoptosis. Furthermore, SUMO-1 modified proteins have recently been linked to cell stress responses, such as oxidative stress response and heat shock response, with increased SUMOylation being neuroprotective in some cases. Several recent studies have linked SUMOylation to the ubiquitin-proteasome system, while other evidence implicates the lysosomal pathway. Other reports depict a direct mechanism whereby sumoylation reduced the aggregation tendency of α-synuclein, and reduced the toxicity. However, the precise role of SUMO-1 in neurodegeneration remains unclear. In this review, we explore the potential direct or indirect role(s) of SUMO-1 in the cellular response to misfolded α-synuclein in neurodegenerative disorders.http://www.mdpi.com/2218-273X/5/3/1697alpha-synucleinParkinson’s diseaseSUMOmultiple system atrophyneurodegenerationautophagy |
| spellingShingle | Shamini Vijayakumaran Mathew B. Wong Helma Antony Dean L. Pountney Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity Biomolecules alpha-synuclein Parkinson’s disease SUMO multiple system atrophy neurodegeneration autophagy |
| title | Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity |
| title_full | Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity |
| title_fullStr | Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity |
| title_full_unstemmed | Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity |
| title_short | Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity |
| title_sort | direct and or indirect roles for sumo in modulating alpha synuclein toxicity |
| topic | alpha-synuclein Parkinson’s disease SUMO multiple system atrophy neurodegeneration autophagy |
| url | http://www.mdpi.com/2218-273X/5/3/1697 |
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