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- Title
Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1-gangliosidosis patients.
- Authors
Maeda, Yuki; Motoyama, Keiichi; Higashi, Taishi; Horikoshi, Yuka; Takeo, Toru; Nakagata, Naomi; Kurauchi, Yuki; Katsuki, Hiroshi; Ishitsuka, Yoichi; Kondo, Yuki; Irie, Tetsumi; Furuya, Hirokazu; Era, Takumi; Arima, Hidetoshi
- Abstract
Objectives 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 ( Cy Ds) 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 Cy Ds 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. Key findings The treatment with methylated Cy Ds, hydroxypropylated Cy Ds and branched Cy Ds decreased GM1-ganglioside levels in EA1 cells at 1 m m for 24 h. Unexpectedly, there was no significant change in the efflux of cholesterol or phospholipids from the cells after treatment with Cy Ds 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 Cy Ds treatment. Conclusions Cy Ds may have the potential as drugs for GM1-gangliosidosis, although the mechanism should be thereafter clarified.
- Subjects
THERAPEUTICS; LYSOSOMAL storage diseases; CYCLODEXTRINS; GANGLIOSIDES; DRUG efficacy; FIBROBLASTS
- Publication
Journal of Pharmacy & Pharmacology, 2015, Vol 67, Issue 8, p1133
- ISSN
0022-3573
- Publication type
Article
- DOI
10.1111/jphp.12405