Gaucher disease (GD) is an inherited lipidstorage disorder caused by deficiency of glucocerebrosidase (GlcCerase) activity and characterized by intralysosomal accumulation of glucocerebroside (glucosylceramide; GlcCer) that leads to dysfunction in multiple organ systems. Miglustat is an iminosugar that reversibly inhibits glucosylceramide synthase and reduces GlcCer biosynthesis[3]. The addition of 10 μM miglustat to COS-7 cell medium leads to 1.3-, 2.1-, 2.3-, 3.6-, and 9.9-fold increase in the activity of S364R, wild-type, N370S, V15M, and M123T GC (β-glucosidase), respectively. These results suggest that miglustat, in addition to the inhibitory effect on CSG (glucosyltransferase), also works as a "chemical chaperone", increasing the activity of acid beta-glucosidase of wild-type and several GC mutated proteins, including the most frequent N370S mutation[4].
To study the effect of Miglustat on the inflammatory response of human astrocytes, results showed that Miglustat suppressed the expression of pro-inflammatory genes.
Cell. 2019 Dec 12;179(7):1483-1498. e22
Peripheral blood mononuclear cells (PBMC)
1 mM
24 hours
To evaluate the effect of Miglustat on cytokine release following SARS-CoV-2 S glycoprotein stimulation, results showed no statistically significant effects on cytokine production.
J Clin Immunol. 2021 Feb;41(2):335-344
NIH3T3 cells
1 mM
24 hours
To evaluate the effect of Miglustat on SARS-CoV-2 S-driven cell-to-cell fusion, results showed no statistically significant differences in syncytia formation frequency or size comparing miglustat-treated samples to untreated controls.
J Clin Immunol. 2021 Feb;41(2):335-344
HEK293T cells
1 mM
24 hours
To evaluate the effect of Miglustat on the N-glycosylation pattern of SARS-CoV-2 S and ACE2 glycoproteins, results showed that Miglustat successfully and specifically modified the N-glycosylation pattern of both glycoproteins.
J Clin Immunol. 2021 Feb;41(2):335-344
hDA neurons
100 μM
3 days
Reduced GlcCer accumulation, restored the ratio of α-syn tetramers and related multimers, and protected neurons from PFF-induced toxicity
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):798-803
SH-SY5Y cells
100 μM
3 days
Reduced intracellular GlcCer levels and restored the ratio of α-syn tetramers and related multimers
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):798-803
Primary 409 cells
100 µM
72 hours
To evaluate the effect of Miglustat on GD2 expression, results showed a significant decrease in GD2 expression
Int J Mol Sci. 2023 Jun 8;24(12):9905
SF8628 cells
100 µM
72 hours
To evaluate the effect of Miglustat on GD2 expression, results showed a significant decrease in GD2 expression
Int J Mol Sci. 2023 Jun 8;24(12):9905
Neonatal rat cardiac fibroblasts (NRCFs)
100 μM and 200 μM
24 hours
To evaluate the effect of Miglustat on ISO-induced cardiac fibroblast activation. Results showed that Miglustat significantly inhibited ISO-induced NRCFs proliferation, ECM deposition, and transdifferentiation.
Mol Med. 2025 Feb 11;31(1):55
Miglustat HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
ISO-induced cardiac fibrosis model
Oral
150 mg/kg and 300 mg/kg
Twice daily for 7 days
To evaluate the effect of Miglustat on ISO-induced cardiac dysfunction and fibrosis. Results showed that Miglustat significantly improved cardiac function, reduced fibrosis area, and suppressed the expression of fibrosis markers.
Mol Med. 2025 Feb 11;31(1):55
NOD mice
Experimental autoimmune encephalomyelitis (EAE)
Oral
600 mg/kg
Once daily for 2 weeks
To study the therapeutic effect of Miglustat on EAE, results showed that Miglustat suppressed EAE progression, reduced axonal loss and demyelination, and decreased the recruitment of pro-inflammatory monocytes.
Cell. 2019 Dec 12;179(7):1483-1498. e22
Mouse
Mcoln1−/− mice
Intraperitoneal injection
300 mg/kg body weight
Daily from P10-P21, then three times a week until the end of the study
Miglustat treatment delays motor deficits, cerebellar microgliosis, and Purkinje cell loss in Mcoln1?/? mice
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