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...
| Päätekijät: | , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
2001
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| Yhteenveto: | 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. |
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