Pathobiochemical effect of acylated steryl-β-glucoside on aggregation and cytotoxicity of α-synuclein

Seigo Usuki, Tetsu Kamitani, Yasuhiro Matsuo, Robert K Yu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cycad seed consumption by the native islanders of Guam is frequently associated with high rates of amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS/PDC); furthermore, accompanying pathological examination often exhibits α-synuclein inclusions in the neurons of the affected brain. Acylated steryl-β-glucoside (ASG) contained in cycad seeds is considered as causative environmental risk factor. We aimed to investigate whether ASG influences aggregation and cell toxicity of α-synuclein. To understand whether ASG is a causative factor in the development of ALS/PDC, soybean-derived ASG was tested for its effect on in vitro aggregation of α-synuclein using Thioflavin-T. ASG was also tested to determine whether it modulates α-synuclein cytotoxicity in yeast cells. In addition, we determined whether an interaction between ASG and α-synuclein occurs in the plasma membrane or cytoplasm using three factors: GM1 ganglioside, small unilamellar vesicles, and ATP. In the present study, we found that ASG-mediated acceleration of α-synuclein aggregation is influenced by the presence of ATP, but not by the presence of GM1. ASG accelerated the α-synuclein aggregation in the cytoplasm. ASG also enhanced α-synuclein-induced cytotoxicity in yeast cells. This study demonstrated that ASG directly enhances aggregation and cytotoxicity of α-synuclein, which are often observed in patients with ALS/PDC. These results, using assays that replicate cytoplasmic conditions, are consistent with the molecular mechanism that cytotoxicity is caused by intracellular α-synuclein fibril formation in neuronal cells.

Original languageEnglish (US)
Pages (from-to)1261-1266
Number of pages6
JournalNeurochemical Research
Volume37
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

Synucleins
Glucosides
Cytotoxicity
Agglomeration
Amyotrophic Lateral Sclerosis
Parkinsonian Disorders
Yeast
Dementia
Seed
Seeds
Cytoplasm
Adenosine Triphosphate
Yeasts
Guam
Cells
G(M1) Ganglioside
Unilamellar Liposomes
Cell Aggregation
Cell membranes
Soybeans

Keywords

  • ALS/PDC
  • Acylated steryl glucoside
  • Aggregation
  • Cytotoxicity
  • Ganglioside
  • α-Synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Pathobiochemical effect of acylated steryl-β-glucoside on aggregation and cytotoxicity of α-synuclein. / Usuki, Seigo; Kamitani, Tetsu; Matsuo, Yasuhiro; Yu, Robert K.

In: Neurochemical Research, Vol. 37, No. 6, 01.06.2012, p. 1261-1266.

Research output: Contribution to journalArticle

Usuki, Seigo ; Kamitani, Tetsu ; Matsuo, Yasuhiro ; Yu, Robert K. / Pathobiochemical effect of acylated steryl-β-glucoside on aggregation and cytotoxicity of α-synuclein. In: Neurochemical Research. 2012 ; Vol. 37, No. 6. pp. 1261-1266.
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