Copper- and iron-induced differential fibril formation in α-synuclein: TEM study

Bharathi,; Indi, S. S.; Rao, K. S.

doi:10.1016/j.neulet.2007.06.052

Cited by 97 publications

(70 citation statements)

References 44 publications

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“…Our studies further confirm that high concentrations of ferric iron can induce α-synuclein aggregation in dopaminergic cell lines, in a dose-and time-dependent way, which is toxic to the cells. This is consistent with other reports that ferrous [21] or ferric iron [22] could promote purified α-synuclein monomer folding, oligomerization, and aggregation in vitro. Co-treatment with iron and other free radical generators, such as dopamine and hydrogen peroxide, can also induce α-synuclein aggregation [20] .…”

Section: Discussionsupporting

confidence: 93%

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Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

Jiang

Song

et al. 2010

Neurosci. Bull.

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Objective Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson's disease. The main component of LB is aggregated α-synuclein, present in the substantia nigra where iron accumulation also occurs. The present study was aimed to study the relationship between iron and α-synuclein aggregation. Methods SK-N-SH cells were treated with different concentrations of ferric iron for 24 h or 48 h. MTT assay was conducted to determine the cell viability.Thioflavine S staining was used to detect α-synuclein aggregation. Results With the increase of iron concentration, the cell viability decreased significantly. At the concentrations of 5 mmol/L and 10 mmol/L, iron induced α-synuclein aggregation more severely than at the concentration of 1 mmol/L. Besides, 48-h treatment-induced aggregation was more severe than that induced by 24-h treatment, at the corresponding iron concentrations. Conclusion Ferric iron can induce α-synuclein aggregation, which is toxic to the cells, in a dose-and time-dependent way.

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Section: Discussionsupporting

confidence: 93%

“…The high concentration of ferric iron has been proved to promote the aggregation of A53T mutant α-synuclein in dopaminergic cells [20] . In vitro studies also show that when incubated with ferrous [21] or ferric iron [22] , α-synuclein folding, oligomerization, and aggregation would be promoted. …”

Section: Introductionmentioning

confidence: 98%

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

Jiang

Song

et al. 2010

Neurosci. Bull.

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“…However, further analysis suggested that a-Syn binds only two Cu(II) ions per monomer: the first of which binds with a dissociation constant in the 0.1-50 lM range and the second with much lower affinity (400-500 lM) (36). Although there is a consensus that a-Syn also binds iron, the reported binding affinities are very different (37)(38)(39). Other metals, such as Mn(II), Co(II), and Ni(II) also bind to a-Syn, however, the affinity for these metals is much lower (K d 1 mM) (37).…”

Section: Metal Binding To Alpha-synucleinmentioning

confidence: 99%

Oligomeric alpha‐synuclein and its role in neuronal death

Brown

2010

IUBMB Life

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SummaryAlpha-synuclein is a natively unfolded protein associated with a number of neurodegenerative disorders that include Parkinson's disease. In the past, research has focused on the fibrillar form of the protein. Current research now indicates that oligomeric alpha-synuclein is the form of the protein most likely to causes neuronal death. Recent research has suggested that a unique oligomer associated with the copper binding capacity of the protein is the neurotoxic form of the protein. This review looks at the evidence for this possibility.

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“…High concentration of ferric iron in dopaminergic cells has been proved to promote the aggregation of A53T mutant alpha-synuclein in cells (Ostrerova-Golts et al 2000). In vitro studies showed that purified alpha-synuclein also aggregated rapidly with application of ferrous (Golts et al 2002) or ferric iron (Bharathi et al 2007). However, the mechanisms underlying iron-induced alpha-synuclein aggregation is still not clear.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Partially Contributes to Iron-Induced Alpha-Synuclein Aggregation in SK-N-SH Cells

Jiang

Song

et al. 2010

Neurotox Res

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Intracellular Lewy body formation is one of the hallmarks of Parkinson's disease (PD). As its main component, aggregated α-synuclein is presented in the substantia nigra, the same region iron accumulation occurs. In this study, the relationship between iron and α-synuclein aggregation was investigated. In the remaining cells, 1 mmol/l ferric and ferrous iron could induce cell loss in SK-N-SH cells and α-synulein aggregation. Pretreatment with 5 μmol/l vitamin E, a potent intracellular reactive oxygen species (ROS) scavenger could totally abolish ROS formation and cell viability reduction induced by ferric and ferrous iron treatment. However, the intracellular α-synuclein aggregation could only be partially alleviated. Due to the predicted iron responsive element (IRE) in the 5'-untranslated region of the human α-synuclein mRNA contains, we observed that α-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more α-synuclein aggregations were observed in cells. The results suggest that iron-induced intracellular aggregated α-synuclein is partially dependent on oxidative stress and iron might also regulate α-synuclein aggregation through the IRE/IRP system.

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Copper- and iron-induced differential fibril formation in α-synuclein: TEM study

Cited by 97 publications

References 44 publications

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells

Oligomeric alpha‐synuclein and its role in neuronal death

Oxidative Stress Partially Contributes to Iron-Induced Alpha-Synuclein Aggregation in SK-N-SH Cells

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