title: Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1-gangliosidosis patients.
abstract: OBJECTIVE
  GM1-gangliosidosis is an inherited disorder characterized by the accumulation of GM1-gangliosides in many tissues and organs, particularly in the brain. Currently, there is no treatment available for patients with ganglioside storage diseases. Therefore, we investigated the effects of cyclodextrins (CyDs) on the GM1-ganglioside level in EA1 cells, fibroblasts from patients with GM1-gangliosidosis.
  
  
  METHODS
  The concentrations of cholesterol and phospholipids in supernatants were determined by Cholesterol E-test Wako and Phospholipid C-test Wako, respectively. The effects of CyDs on GM1-ganglioside levels in EA1 cells using fluorescence-labelled cholera toxin B-subunit, which can bind to GM1-gangliosides specifically, were investigated by flow cytometry and confocal laser scanning microscopy.
  
  
  RESULTS
  The treatment with methylated CyDs, hydroxypropylated CyDs and branched CyDs decreased GM1-ganglioside levels in EA1 cells at 1 mm for 24 h. Unexpectedly, there was no significant change in the efflux of cholesterol or phospholipids from the cells after treatment with CyDs under the same experimental conditions, indicating that the efflux of membrane components is not associated with down-regulation of GM1-ganglioside levels in EA1 cells upon CyDs treatment.
  
  
  CONCLUSIONS
  CyDs may have the potential as drugs for GM1-gangliosidosis, although the mechanism should be thereafter clarified.
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Program for Leading Graduate Schools 'HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program', Kumamoto University, Kumamoto, Japan.
authors: Yuki
authors: Y
authors: Maeda
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Keiichi
authors: K
authors: Motoyama
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Taishi
authors: T
authors: Higashi
authors: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
authors: Yuka
authors: Y
authors: Horikoshi
authors: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
authors: Toru
authors: T
authors: Takeo
authors: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
authors: Naomi
authors: N
authors: Nakagata
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Program for Leading Graduate Schools 'HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program', Kumamoto University, Kumamoto, Japan.
authors: Yuki
authors: Y
authors: Kurauchi
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Hiroshi
authors: H
authors: Katsuki
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yoichi
authors: Y
authors: Ishitsuka
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yuki
authors: Y
authors: Kondo
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Program for Leading Graduate Schools 'HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program', Kumamoto University, Kumamoto, Japan.
authors: Tetsumi
authors: T
authors: Irie
authors: Department of Neurology, Kochi Medical School, Kochi University, Kochi, Japan.
authors: Hirokazu
authors: H
authors: Furuya
authors: Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Takumi
authors: T
authors: Era
authors: Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.|Program for Leading Graduate Schools 'HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program', Kumamoto University, Kumamoto, Japan.
authors: Hidetoshi
authors: H
authors: Arima
mesh_terms: D001343:Autophagy / Q000187:drug effects; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D016537:Gangliosidosis, GM1 / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism
chemical_list: D003505:Cyclodextrins; D010743:Phospholipids; D005677:G(M1) Ganglioside; D002784:Cholesterol
keywords: GM1-gangliosidosis; cyclodextrins; fibroblasts; lysosomes