Lowering effect of dimethyl-α-cyclodextrin on GM1-ganglioside accumulation in GM1-gangliosidosis model cells and in brain of β-galactosidase-knockout mice

  • Yuki Maeda
  • Keiichi Motoyama
  • Taishi Higashi
  • Risako Onodera
  • Toru Takeo
  • Naomi Nakagata
  • Yuki Kurauchi
  • Hiroshi Katsuki
  • Yoichi Ishitsuka
  • Yuki Kondo
  • Tetsumi Irie
  • Takumi Era
  • Hidetoshi ArimaEmail author
Original Article


GM1-gangliosidosis (GM1G) is caused by a deficiency of β-galactosidase, resulting in the excessive accumulation of GM1-ganglioside (GM1) in lysosomes of cells, particularly in the nerve cells (neurons). There is no treatment available for patients with GM1G. Meanwhile, cyclodextrins (CyDs) are cyclic oligosaccharides, which are widely used in the pharmaceutical field. We previously reported that 2, 6-di-O-methyl-α-CyD (DM-α-CyD) extracted phospholipids from lipid rafts, which are abundant with sphingolipids including GM1. Therefore, in the present study, we investigated the effects of α-CyDs on GM1 levels in GM1G model cells and in brain of GM1G model mice. The interaction of DM-α-CyD with GM1 was stronger than that of 2-hydroxypropyl-α-CyD. Additionally, DM-α-CyD significantly reduced GM1 levels in GM1G model cells at 1 mM for 24 h. Furthermore, DM-α-CyD decreased GM1 levels in brain after an intraventricular administration to GM1G model mice without any significant side effects. These results strongly suggest that DM-α-CyD decreased the accumulation of GM1 in not only GM1G model cells but also GM1G model mice. Collectively, DM-α-CyD may have the potential as a therapeutic drug for GM1G.


Cyclodextrins GM1-gangliosidosis GM1-ganglioside, cholesterol, lysosomes 



This work was supported by Grant-in-Aid for JSPS Research Fellow (16J11970) and Health and Labor Sciences Research Grant in Japan (17bk01040015h0005).

Compliance with ethical standards

Conflict of interest

There is no conflict of interest in this paper.

Supplementary material

10847_2018_835_MOESM1_ESM.pptx (65 kb)
Supplementary Figure S1 TUNEL analysis of brain after intraventricular injection of DM-α-CyD to WT mice. Twenty four h after intraventricular injection of 1 μL of solution containing 431.6 mM DM-α-CyD to WT mice, the brain was collected and 7 μm sequential coronal sections were prepared. TUNEL assay was performed by using the Apoptosis in Situ Detection Kit. The images were representative data of 3 experiments. (PPTX 65 KB)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Yuki Maeda
    • 1
    • 2
  • Keiichi Motoyama
    • 1
  • Taishi Higashi
    • 1
  • Risako Onodera
    • 1
  • Toru Takeo
    • 3
  • Naomi Nakagata
    • 3
  • Yuki Kurauchi
    • 1
  • Hiroshi Katsuki
    • 1
  • Yoichi Ishitsuka
    • 1
  • Yuki Kondo
    • 1
  • Tetsumi Irie
    • 1
    • 2
  • Takumi Era
    • 4
  • Hidetoshi Arima
    • 1
    • 2
    Email author
  1. 1.Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Program for Leading Graduate Schools “HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program”Kumamoto UniversityKumamotoJapan
  3. 3.Center for Animal Resources and DevelopmentKumamoto UniversityKumamotoJapan
  4. 4.Department of Cell Modulation, Institute of Molecular Embryology and GeneticsKumamoto UniversityKumamotoJapan

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