ISSN: 2641-9459
Authors: Koon AC*
Aggregation of misfolded proteins is a hallmark of many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and polyglutamine (polyQ) diseases. Clearance of misfolded proteins in the cell relies on the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system. Since their discoveries, the UPS and autophagy were once thought to be independent of each other in terms of components, mechanisms and substrate selectivity. The UPS was believed to be responsible for degrading soluble proteins, whereas autophagy for degrading insoluble protein aggregates. However, recent studies have demonstrated that the insoluble protein aggregates may not be cytotoxic. By contrast, after deaggregation, multimers and microaggregates may still be present in the cell causing cytotoxicity. The UPS is incapable of degrading these soluble and semi-soluble species, and the vital task of degradation these toxic species rests upon the autophagy-lysosome system. Therefore, apart from degrading the visible protein aggregates, autophagy is also responsible for eliminating these “invisible dangers†to protect the cell in neurodegenerative diseases.
Keywords: Autophagy; Protein Aggregation; Polyglutamine; Neurodegeneration
