Next Article in Journal
RNA Binding Proteins that Control Human Papillomavirus Gene Expression
Next Article in Special Issue
Mechanisms of Alpha-Synuclein Action on Neurotransmission: Cell-Autonomous and Non-Cell Autonomous Role
Previous Article in Journal / Special Issue
Effects of Trehalose on Thermodynamic Properties of Alpha-synuclein Revealed through Synchrotron Radiation Circular Dichroism
Review

Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies

1
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal
2
ICVS/3B's—PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Stephan N. Witt
Biomolecules 2015, 5(2), 735-757; https://doi.org/10.3390/biom5020735
Received: 12 March 2015 / Revised: 13 April 2015 / Accepted: 27 April 2015 / Published: 4 May 2015
Insoluble and fibrillar forms of α-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. α-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. α-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for α-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuins’s role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to rescue cells from α-synuclein toxicity. The controversial reports on the potential role of sirtuins in the degradation of α-synuclein will be discussed. Connection between sirtuins and proteolytic systems is definitely worth of further studies to increase the knowledge that will allow its proper exploration as new avenue to fight synucleinopathies. View Full-Text
Keywords: α-synuclein; ubiquitin-proteasome system; chaperone-mediated autophagy; (macro)autophagy; aging; mitochondria; sirtuins α-synuclein; ubiquitin-proteasome system; chaperone-mediated autophagy; (macro)autophagy; aging; mitochondria; sirtuins
Show Figures

Figure 1

MDPI and ACS Style

Sampaio-Marques, B.; Ludovico, P. Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies. Biomolecules 2015, 5, 735-757. https://doi.org/10.3390/biom5020735

AMA Style

Sampaio-Marques B, Ludovico P. Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies. Biomolecules. 2015; 5(2):735-757. https://doi.org/10.3390/biom5020735

Chicago/Turabian Style

Sampaio-Marques, Belém, and Paula Ludovico. 2015. "Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies" Biomolecules 5, no. 2: 735-757. https://doi.org/10.3390/biom5020735

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop