Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies
Seoul National University · Rappaport Family Institute for Research in the Medical Sciences
Abstract
Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by…
Citation impact
- FWCI
- 51.65
- Percentile
- 100%
- References
- 235
Authors
2Topics & keywords
- Proteasome
- Aggresome
- Cell biology
- Protein aggregation
- Protein folding
- Ubiquitin
- Neurodegeneration
- Biology
Funding
- ICIsrael Cancer Research Fund
- DMDr. Miriam and Sheldon G. Adelson Medical Research Foundation
- NRNational Research Foundation
- SNSeoul National University
- MOMinistry of Science, ICT and Future PlanningAward: NRF-2013R1A2A2A01014170
- ISIsrael Science FoundationAward: Grant1775/12
- NINational Institutes of HealthAward: HL083365
- ICIsraeli Centers for Research Excellence
- PAPlanning and Budgeting Committee of the Council for Higher Education of Israel