Nitration inhibits fibrillation of human α‐synuclein in vitro by formation of soluble oligomers
Open Access
- 15 April 2003
- journal article
- Published by Wiley in FEBS Letters
- Vol. 542 (1-3) , 147-152
- https://doi.org/10.1016/s0014-5793(03)00367-3
Abstract
The aggregation of α‐synuclein in dopaminergic neurons is a critical factor in the etiology of Parkinson's disease (PD). Oxidative and nitrative stress is also implicated in PD. We examined the effect of nitration on the propensity of α‐synuclein to fibrillate in vitro. Fibril formation of α‐synuclein was completely inhibited by nitration, due to the formation of stable soluble oligomers (apparently octamers). More importantly the presence of sub‐stoichiometric concentrations of nitrated α‐synuclein led to inhibition of fibrillation of non‐modified α‐synuclein. These observations suggest that nitration of soluble α‐synuclein may be a protective factor in PD, rather than a causative one.Keywords
This publication has 43 references indexed in Scilit:
- Annular α-Synuclein Protofibrils Are Produced When Spherical Protofibrils Are Incubated in Solution or Bound to Brain-Derived MembranesBiochemistry, 2002
- Biophysical Properties of the Synucleins and Their Propensities to FibrillateJournal of Biological Chemistry, 2002
- Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicityJournal of Molecular Biology, 2001
- Conformational properties of α-synuclein in its free and lipid-associated states 1 1Edited by P. E. WrightJournal of Molecular Biology, 2001
- Intrinsically unstructured proteins: re-assessing the protein structure-function paradigmJournal of Molecular Biology, 1999
- Synthetic filaments assembled from C‐terminally truncated α‐synucleinFEBS Letters, 1998
- AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's diseaseNature Genetics, 1998
- Mutation in the α-Synuclein Gene Identified in Families with Parkinson's DiseaseScience, 1997
- The importance of being unfoldedNature, 1997
- NACP, A Protein Implicated in Alzheimer's Disease and Learning, Is Natively UnfoldedBiochemistry, 1996