Back to Search
Start Over
Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Mar 11; Vol. 280 (10), pp. 9678-90. Date of Electronic Publication: 2004 Dec 21. - Publication Year :
- 2005
-
Abstract
- Oxidative stress is implicated in a number of neuro-degenerative diseases and is associated with the selective loss of dopaminergic neurons of the substantia nigra in Parkinson's disease. The role of alpha-synuclein as a potential target of intracellular oxidants has been demonstrated by the identification of posttranslational modifications of synuclein within intracellular aggregates that accumulate in Parkinson's disease brains, as well as the ability of a number of oxidative insults to induce synuclein oligomerization. The relationship between these relatively small soluble oligomers, potentially neurotoxic synuclein protofibrils, and synuclein filaments remains unclear. We have found that metal-catalyzed oxidation of alpha-synuclein inhibited formation of synuclein filaments with a concomitant accumulation of beta sheet-rich oligomers that may represent synuclein protofibrils. Similar results with a number of oxidative and enzymatic treatments suggest that the covalent association of synuclein into higher molecular mass oligomers/protofibrils represents an alternate pathway from filament formation and renders synuclein less prone to proteasomal degradation.
- Subjects :
- Actin Cytoskeleton ultrastructure
Brain metabolism
Humans
Iron metabolism
Kinetics
Macromolecular Substances chemistry
Macromolecular Substances metabolism
Models, Biological
Oxidants metabolism
Oxidation-Reduction
Oxidative Stress
Parkinson Disease metabolism
Protein Processing, Post-Translational
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Synucleins
alpha-Synuclein
Metals metabolism
Nerve Tissue Proteins chemistry
Nerve Tissue Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15615715
- Full Text :
- https://doi.org/10.1074/jbc.M409946200