RT Journal Article
T1 Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway
A1 Lucas Rodríguez, Patricia Antonia
A1 Brokate Llanos, Ana María
A1 Hernández Curiel, José Manuel
A1 Murdoch, Piedad Del Socorro
A1 Garzón, Andrés
A1 Carrión Rodríguez, Ángel Manuel
A1 Muñoz Ruiz, Manuel Jesús
K1 C. elegans
K1 Insulin Pathway
K1 Model animals
K1 Monosaccharides
K1 Rare disease
K1 Type III galactosemia
K1 UDP-galactose-4-epimerase
AB Type III galactosemia is characterized by the inability to metabolize galactose due to deficiency of the UDP-galactose-4-epimerase (GALE) gene, which catalyzes the interconversion of UDP-Galactose and UDP-Glucose. Additionally, GALE interconverts UDP-N-Acetylgalactosamine and UDP-N-Acetylglucosamine. These four sugars are needed for glycosylation of biomolecules. GALE deletion is considered lethal, and all described patients carry hypomorphic mutations. Symptoms are diverse and can range from mild to severe, without effective treatment. We have previously generated a Caenorhabditis elegans model for type III galactosemia, which carries a hypomorphic mutation in the GALE gene homologue. In this model, we observed that the symptoms varied depending on the diet. The aim of this work is to identify which dietary metabolites might alleviate the symptoms of type III galactosemia. To identify the molecules responsible, we used a C. elegans model of type III galactosemia and a mouse model to test whether the respond to the treatment is conserved in mammals and thus could be a putative intervention in patients. We found that high levels of monosaccharides in the diet is responsible for the beneficial effect in the C. elegans model. This intervention generates an increase of gale-1 expression through activation of the insulin pathway which may explain the reduction of the symptoms in animals carrying hypomorphic mutations. The increase of the GALE gene expression after monosaccharides treatment is also conserved in mammals and if maintained in humans, monosaccharide treatment combined with monitorization of GALE expression could be included in the management of patients with type III galactosemia.
PB Elsevier
YR 2024
FD 2024-12
LK https://hdl.handle.net/10433/22855
UL https://hdl.handle.net/10433/22855
LA en
NO Lucas-Rodríguez, P., Brokate-Llanos, A. M., Hernandez-Curiel, J. M., Murdoch, P. del S., Garzón, A., Carrión, A., & Muñoz, M. J. (2024). Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway. Biomedicine & Pharmacotherapy, 181, 117677-. https://doi.org/10.1016/j.biopha.2024.117677
NO Dpto Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide
NO Departamento de Biología Molecular e Ingeniería Bioquímica, Universidad Pablo de Olavide
NO Centro Andaluz de Biología del Desarrollo (CABD)
NO Departamento de Bioquímica Vegetal y Biología Molecular, Facultad de Biología, Universidad de Sevilla,
DS RIO
RD Apr 23, 2026