Fingolimod Rescues Demyelination in a Mouse Model of Krabbe's Disease

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Sibylle BéchetKumlesh K Dev

Abstract

Krabbe's disease is an infantile neurodegenerative disease, which is affected by mutations in the lysosomal enzyme galactocerebrosidase, leading to the accumulation of its metabolite psychosine. We have shown previously that the S1P receptor agonist fingolimod (FTY720) attenuates psychosine-induced glial cell death and demyelination both in vitro and ex vivo models. These data, together with a lack of therapies for Krabbe's disease, prompted the current preclinical study examining the effects of fingolimod in twitcher mice, a murine model of Krabbe's disease. Twitcher mice, both male and female, carrying a natural mutation in the galc gene were given fingolimod via drinking water (1 mg/kg/d). The direct impact of fingolimod administration was assessed via histochemical and biochemical analysis using markers of myelin, astrocytes, microglia, neurons, globoid cells, and immune cells. The effects of fingolimod on twitching behavior and life span were also demonstrated. Our results show that treatment of twitcher mice with fingolimod significantly rescued myelin levels compared with vehicle-treated animals and also regulated astrocyte and microglial reactivity. Furthermore, nonphosphorylated neurofilament levels were decreased, ind...Continue Reading

Citations

Jul 23, 2020·Drugs in R&D·Pablo BascuñanaJens Pahnke
Jun 18, 2020·International Journal of Molecular Sciences·Kim M A De Kleijn, Gerard J M Martens
Aug 8, 2021·International Journal of Molecular Sciences·Bhakta Prasad Gaire, Ji-Woong Choi

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
fluorescence microscopy
electrophoresis

Software Mentioned

GraphPad Prism
Image studio
Imaris
GraphPad
ImageJ

Related Concepts

Related Feeds

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Yuichiro Hashi, Takayuki Kondo
Journal of Inherited Metabolic Disease
Y EtoK M Maekawa
Clinical Pharmacokinetics
Olivier J DavidRobert Schmouder
Clinical Neurology and Neurosurgery
Katja Thomas, Tjalf Ziemssen
© 2021 Meta ULC. All rights reserved