Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity
Abstractα-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. View Full-Text
Share & Cite This Article
Vijayakumaran, S.; Wong, M.B.; Antony, H.; Pountney, D.L. Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity. Biomolecules 2015, 5, 1697-1716.
Vijayakumaran S, Wong MB, Antony H, Pountney DL. Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity. Biomolecules. 2015; 5(3):1697-1716.Chicago/Turabian Style
Vijayakumaran, Shamini; Wong, Mathew B.; Antony, Helma; Pountney, Dean L. 2015. "Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity." Biomolecules 5, no. 3: 1697-1716.