Browsing by Author "Campos, F."

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    c-Abl activates RIPK3 signaling in Gaucher disease
    (2021) Yañez Henríquez, María José; Campos, F.; Marín Marín, Tamara Alejandra; Klein Posternack, Andrés David; Futerman, A. H.; Álvarez, Alejandra R.; Zanlungo Matsuhiro, Silvana
    Gaucher disease (GD) is caused by homozygous mutations in the GBA1 gene, which encodes the lysosomal β-glucosidase (GBA) enzyme. GD affects several organs and tissues, including the brain in certain variants of the disease. Heterozygous GBA1 variants are a major genetic risk factor for developing Parkinson's disease. The RIPK3 kinase is relevant in GD and its deficiency improves the neurological and visceral symptoms in a murine GD model. RIPK3 mediates necroptotic-like cell death: it is unknown whether the role of RIPK3 in GD is the direct induction of necroptosis or if it has a more indirect function by mediating necrosis-independent. Also, the mechanisms that activate RIPK3 in GD are currently unknown. In this study, we show that c-Abl tyrosine kinase participates upstream of RIPK3 in GD. We found that the active, phosphorylated form of c-Abl is increased in several GD models, including patient's fibroblasts and GBA null mice. Furthermore, its pharmacological inhibition with the FDA-approved drug Imatinib decreased RIPK3 signaling. We found that c-Abl interacts with RIPK3, that RIPK3 is phosphorylated at a tyrosine site, and that this phosphorylation is reduced when c-Abl is inhibited. Genetic ablation of c-Abl in neuronal GD and GD mice models significantly reduced RIPK3 activation and MLKL downstream signaling. These results showed that c-Abl signaling is a new upstream pathway that activates RIPK3 and that its inhibition is an attractive therapeutic approach for the treatment of GD.
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    Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5
    (2020) Abrigo, J.; Campos, F.; González, F.; Aguirre, F.; González, A.; Huerta Salgado, C.; Conejeros, S.; Simon, F.; Arrese, Marco; Cabello Verrugio, Claudio Alejandro; Elorza, A. A.; Cabello Verrugio, Claudio Alejandro
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    Visualization tools for understanding a complex code from a real application
    (2009) Campos, F.; Cortazar, E.; Eterovic, Y.; Ramirez, L.; Tejos Nunez, Cristian Andres; Irarrazaval, P.
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    Visualization tools for understanding a complex code from a real application
    (2009) Campos, F.; Cortazar, E.; Eterovic, Y.; Ramirez, L.; Tejos Nunez, Cristian Andres; Irarrazaval, P.