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

Neurosci Bull. 2010 Jun;26(3):205-10. doi: 10.1007/s12264-010-1117-7.


Objective: Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson's disease. The main component of LB is aggregated alpha-synuclein, present in the substantia nigra where iron accumulation also occurs. The present study aimed to study the relationship between iron and alpha-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 alpha-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 alpha-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 alpha-synuclein aggregation, which is toxic to the cells, in a dose- and time-dependent way.

目的: 帕金森氏病的一个重要标志是胞浆内路易小体的形成。 路易小体的主要成分是α- 突触核蛋白的聚集体, 它和铁的积聚一同存在于黒质区。 本实验旨在研究铁和α- 突触核蛋白聚集的关系。

方法: SK-N-SH 细胞在不同浓度的三价铁作用下, 分别孵育24 h 或48 h, 用MTT 法和硫磺素S 染色法分别检测细胞存活率、 观察α- 突触核蛋白的聚集情况。

结果: 随着铁离子浓度的升高, 细胞存活率显著下降。 其中5 mmol/L 和10 mmol/L 三价铁引起的α- 突触核蛋白的聚集相较于1 mmol/L 的三价铁引起的聚集更为严重。 此外, 在同一浓度的三价铁作用下, 孵育48 h引起的聚集比孵育24 h引起的聚集更严重。

结论: 铁离子诱发的α-突触核蛋白的聚集具有剂量和时间的依赖性, 并且α- 突触核蛋白的聚集介导了铁的毒性作用。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzothiazoles
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / toxicity*
  • Humans
  • Iron / administration & dosage
  • Iron / toxicity*
  • Thiazoles
  • Time Factors
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / metabolism*


  • Benzothiazoles
  • Ferric Compounds
  • Thiazoles
  • alpha-Synuclein
  • thioflavin T
  • Iron