Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure - PubMed (original) (raw)
. 2001 Nov 23;276(47):44284-96.
doi: 10.1074/jbc.M105343200. Epub 2001 Sep 11.
Affiliations
- PMID: 11553618
- DOI: 10.1074/jbc.M105343200
Free article
Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure
V N Uversky et al. J Biol Chem. 2001.
Free article
Abstract
Parkinson's disease involves the aggregation of alpha-synuclein to form fibrils, which are the major constituent of intracellular protein inclusions (Lewy bodies and Lewy neurites) in dopaminergic neurons of the substantia nigra. Occupational exposure to specific metals, especially manganese, copper, lead, iron, mercury, zinc, aluminum, appears to be a risk factor for Parkinson's disease based on epidemiological studies. Elevated levels of several of these metals have also been reported in the substantia nigra of Parkinson's disease subjects. We examined the effect of various metals on the kinetics of fibrillation of recombinant alpha-synuclein and in inducing conformational changes, as monitored by biophysical techniques. Several di- and trivalent metal ions caused significant accelerations in the rate of alpha-synuclein fibril formation. Aluminum was the most effective, along with copper(II), iron(III), cobalt(III), and manganese(II). The effectiveness correlated with increasing ion charge density. A correlation was noted between efficiency in stimulating fibrillation and inducing a conformational change, ascribed to formation of a partially folded intermediate. The potential for ligand bridging by polyvalent metal ions is proposed to be an important factor in the metal-induced conformational changes of alpha-synuclein. The results indicate that low concentrations of some metals can directly induce alpha-synuclein fibril formation.
Similar articles
- Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson's disease.
Uversky VN, Li J, Bower K, Fink AL. Uversky VN, et al. Neurotoxicology. 2002 Oct;23(4-5):527-36. doi: 10.1016/s0161-813x(02)00067-0. Neurotoxicology. 2002. PMID: 12428725 - Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins.
Uversky VN, Li J, Souillac P, Millett IS, Doniach S, Jakes R, Goedert M, Fink AL. Uversky VN, et al. J Biol Chem. 2002 Apr 5;277(14):11970-8. doi: 10.1074/jbc.M109541200. Epub 2002 Jan 25. J Biol Chem. 2002. PMID: 11812782 - Methionine oxidation, alpha-synuclein and Parkinson's disease.
Glaser CB, Yamin G, Uversky VN, Fink AL. Glaser CB, et al. Biochim Biophys Acta. 2005 Jan 17;1703(2):157-69. doi: 10.1016/j.bbapap.2004.10.008. Epub 2004 Nov 25. Biochim Biophys Acta. 2005. PMID: 15680224 Review. - Challenges and complexities of alpha-synuclein toxicity: new postulates in unfolding the mystery associated with Parkinson's disease.
Hegde ML, Jagannatha Rao KS. Hegde ML, et al. Arch Biochem Biophys. 2003 Oct 15;418(2):169-78. doi: 10.1016/j.abb.2003.08.015. Arch Biochem Biophys. 2003. PMID: 14522588 Review.
Cited by
- Fluorogenic tagging methodology applied to characterize oxidized tyrosine and phenylalanine in an immunoglobulin monoclonal antibody.
Zhou S, Mozziconacci O, Kerwin BA, Schöneich C. Zhou S, et al. Pharm Res. 2013 May;30(5):1311-27. doi: 10.1007/s11095-012-0970-7. Epub 2013 Feb 15. Pharm Res. 2013. PMID: 23412915 - Mechanism of copper(II)-induced misfolding of Parkinson's disease protein.
Rose F, Hodak M, Bernholc J. Rose F, et al. Sci Rep. 2011;1:11. doi: 10.1038/srep00011. Epub 2011 Jun 14. Sci Rep. 2011. PMID: 22355530 Free PMC article. - Phosphorylation of α-Synuclein at Y125 and S129 alters its metal binding properties: implications for understanding the role of α-Synuclein in the pathogenesis of Parkinson's Disease and related disorders.
Lu Y, Prudent M, Fauvet B, Lashuel HA, Girault HH. Lu Y, et al. ACS Chem Neurosci. 2011 Nov 16;2(11):667-75. doi: 10.1021/cn200074d. Epub 2011 Sep 14. ACS Chem Neurosci. 2011. PMID: 22860160 Free PMC article. - Copper(II) Can Kinetically Trap Arctic and Italian Amyloid-β40 as Toxic Oligomers, Mimicking Cu(II) Binding to Wild-Type Amyloid-β42: Implications for Familial Alzheimer's Disease.
Tian Y, Shang Q, Liang R, Viles JH. Tian Y, et al. JACS Au. 2024 Feb 6;4(2):578-591. doi: 10.1021/jacsau.3c00687. eCollection 2024 Feb 26. JACS Au. 2024. PMID: 38425915 Free PMC article. - The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy.
Gaeta A, Hider RC. Gaeta A, et al. Br J Pharmacol. 2005 Dec;146(8):1041-59. doi: 10.1038/sj.bjp.0706416. Br J Pharmacol. 2005. PMID: 16205720 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous