Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8550106 | NeuroToxicology | 2018 | 16 Pages |
Abstract
Protein homeostasis is essential for the wellbeing of several cellular systems. Post-translational modifications (PTM) coordinate various pathways in response to abnormal aggregation of proteins in neurodegenerative disease states. In the presence of accumulating misfolded proteins and toxic aggregates, the small ubiquitin-like modifier (SUMO) is associated with various substrates, including chaperones and other recruited factors, for refolding and for clearance via proteolytic systems, such as the ubiquitin-proteasome pathway (UPS), chaperone-mediated autophagy (CMA) and macroautophagy. However, these pathological aggregates are also known to inhibit both the UPS and CMA, further creating a toxic burden on cells. This review suggests that re-routing cytotoxic aggregates towards selective macroautophagy by modulating the SUMO pathway could provide new mechanisms towards neuroprotection.
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Authors
Shamini Vijayakumaran, Dean L. Pountney,