Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-05-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/5/2/735 |
| _version_ | 1819091712397541376 |
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| author | Belém Sampaio-Marques Paula Ludovico |
| author_facet | Belém Sampaio-Marques Paula Ludovico |
| author_sort | Belém Sampaio-Marques |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T22:44:05Z |
| format | Article |
| id | doaj.art-1de36acf718b42f4821b4a2adf80ba25 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-21T22:44:05Z |
| publishDate | 2015-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-1de36acf718b42f4821b4a2adf80ba252022-12-21T18:47:46ZengMDPI AGBiomolecules2218-273X2015-05-015273575710.3390/biom5020735biom5020735Sirtuins and Proteolytic Systems: Implications for Pathogenesis of SynucleinopathiesBelém Sampaio-Marques0Paula Ludovico1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, PortugalLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, PortugalInsoluble 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.http://www.mdpi.com/2218-273X/5/2/735α-synucleinubiquitin-proteasome systemchaperone-mediated autophagy(macro)autophagyagingmitochondriasirtuins |
| spellingShingle | Belém Sampaio-Marques Paula Ludovico Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies Biomolecules α-synuclein ubiquitin-proteasome system chaperone-mediated autophagy (macro)autophagy aging mitochondria sirtuins |
| title | Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies |
| title_full | Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies |
| title_fullStr | Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies |
| title_full_unstemmed | Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies |
| title_short | Sirtuins and Proteolytic Systems: Implications for Pathogenesis of Synucleinopathies |
| title_sort | sirtuins and proteolytic systems implications for pathogenesis of synucleinopathies |
| topic | α-synuclein ubiquitin-proteasome system chaperone-mediated autophagy (macro)autophagy aging mitochondria sirtuins |
| url | http://www.mdpi.com/2218-273X/5/2/735 |
| work_keys_str_mv | AT belemsampaiomarques sirtuinsandproteolyticsystemsimplicationsforpathogenesisofsynucleinopathies AT paulaludovico sirtuinsandproteolyticsystemsimplicationsforpathogenesisofsynucleinopathies |