Protein Quality Control Pathways at the Crossroad of SynucleinopathiesDe Mattos, E. P., Wentink, A., Nussbaum-Krammer, C., Hansen, C., Bergink, S., Melki, R. & Kampinga, H. H., 3-Apr-2020, In : Journal of Parkinson's Disease. 10, 2, p. 369-382 14 p.
Research output: Contribution to journal › Review article › Academic › peer-review
The pathophysiology of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and many others converge at alpha-synuclein (α-Syn) aggregation. Although it is still not entirely clear what precise biophysical processes act as triggers, cumulative evidence points towards a crucial role for protein quality control (PQC) systems in modulating α-Syn aggregation and toxicity. These encompass distinct cellular strategies that tightly balance protein production, stability, and degradation, ultimately regulating α-Syn levels. Here, we review the main aspects of α-Syn biology, focusing on the cellular PQC components that are at the heart of recognizing and disposing toxic, aggregate-prone α-Syn assemblies: molecular chaperones and the ubiquitin-proteasome system and autophagy-lysosome pathway, respectively. A deeper understanding of these basic protein homeostasis mechanisms might contribute to the development of new therapeutic strategies envisioning the prevention and/or enhanced degradation of α-Syn aggregates.
|Number of pages||14|
|Journal||Journal of Parkinson's Disease|
|Early online date||24-Jan-2020|
|Publication status||Published - 3-Apr-2020|
- Alpha-synuclein, synucleinopathies, protein homeostasis, protein aggregation, molecular chaperones, ubiquitin-proteasome system, autophagy, MUTANT ALPHA-SYNUCLEIN, CHAPERONE-MEDIATED AUTOPHAGY, MULTIPLE SYSTEM ATROPHY, GLIAL CYTOPLASMIC INCLUSIONS, HEAT-SHOCK PROTEINS, PARKINSONS-DISEASE, FIBRIL FORMATION, IMPAIRS MACROAUTOPHAGY, LYSOSOMAL DEGRADATION, MOLECULAR CHAPERONES