α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome
α-Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over-expression of wild-type human α-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this...
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1826299620928520192 |
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| author | Tofaris, G Layfield, R Spillantini, MG |
| author_facet | Tofaris, G Layfield, R Spillantini, MG |
| author_sort | Tofaris, G |
| collection | OXFORD |
| description | α-Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over-expression of wild-type human α-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of α-synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified α-synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin-independent mechanism of proteasomal degradation for α-synuclein and other natively unfolded proteins. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. |
| first_indexed | 2024-03-07T05:04:43Z |
| format | Journal article |
| id | oxford-uuid:d982f5f4-d6af-4c74-8ab8-c198170e6cf9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:04:43Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:d982f5f4-d6af-4c74-8ab8-c198170e6cf92022-03-27T08:56:25Zα-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasomeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d982f5f4-d6af-4c74-8ab8-c198170e6cf9EnglishSymplectic Elements at Oxford2001Tofaris, GLayfield, RSpillantini, MGα-Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over-expression of wild-type human α-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of α-synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified α-synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin-independent mechanism of proteasomal degradation for α-synuclein and other natively unfolded proteins. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. |
| spellingShingle | Tofaris, G Layfield, R Spillantini, MG α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title | α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title_full | α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title_fullStr | α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title_full_unstemmed | α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title_short | α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome |
| title_sort | α synuclein metabolism and aggregation is linked to ubiquitin independent degradation by the proteasome |
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