Effects of cyclodextrins on GM1‐gangliosides in fibroblasts from GM1‐gangliosidosis patients. (7th April 2015)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of pharmacy and pharmacology. Volume 67:Number 8(2015:Aug.)
• Page Start: 1133
• Page End: 1142
• Publication Date: 2015-04-07
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12405
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12405-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="jphp12405-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="jphp12405-sec-0003" sec-type="section"> <title>Key findings</title> <p>The treatment with methylated CyDs, hydroxypropylated CyDs and branched CyDs decreased GM1‐ganglioside levels in EA1 cells at 1 m<sc>m</sc> 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.</p> </sec> <sec id="jphp12405-sec-0004" sec-type="section"> <title>Conclusions</title> <p>CyDs may have the potential as drugs for GM1‐gangliosidosis, although the mechanism should be thereafter clarified.</p> </sec> </abstract>