Search

Your search keyword '"Carlos Sindreu"' showing total 2 results
Start Over Author "Carlos Sindreu" Journal science signaling
2 results on '"Carlos Sindreu"'

1. L-Serine dietary supplementation is associated with clinical improvement of loss-of-function

Author

David, Soto, Mireia, Olivella, Cristina, Grau, Judith, Armstrong, Clara, Alcon, Xavier, Gasull, Ana, Santos-Gómez, Sílvia, Locubiche, Macarena, Gómez de Salazar, Roberto, García-Díaz, Esther, Gratacòs-Batlle, David, Ramos-Vicente, Emeline, Chu-Van, Benoit, Colsch, Víctor, Fernández-Dueñas, Francisco, Ciruela, Àlex, Bayés, Carlos, Sindreu, Anna, López-Sala, Àngels, García-Cazorla, and Xavier, Altafaj

Subjects
Male, Models, Molecular, Brain Diseases, N-Methylaspartate, Motor Activity, Receptors, N-Methyl-D-Aspartate, Mice, Cognition, Loss of Function Mutation, Dietary Supplements, Rett Syndrome, Serine, Animals, Humans, Child
Abstract

Autosomal dominant mutations in

Published
2019

2. <scp>l</scp> -Serine dietary supplementation is associated with clinical improvement of loss-of-function GRIN2B -related pediatric encephalopathy

Author

Roberto García-Díaz, Benoit Colsch, Mireia Olivella, Francisco Ciruela, Sílvia Locubiche, Macarena Gómez de Salazar, Àlex Bayés, Anna López-Sala, Xavier Altafaj, Esther Gratacòs-Batlle, Ana Santos-Gómez, Xavier Gasull, Angels García-Cazorla, Víctor Fernández-Dueñas, David Ramos-Vicente, Judith Armstrong, Clara Alcon, Emeline Chu-Van, Carlos Sindreu, Cristina Grau, David Soto, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Catalonia, Partenaires INRAE, Hospital Sant Joan de Déu, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Universidad santiago de cali, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona (UAB), Université Paris Saclay (COmUE), La Marato [20140210], Miguel Servet Program (ISCIII) [CPII16/00021], MINECOSpanish Ministry of Economy & Competitiveness [PCIN-2014-105, BFU2012-34398, BFU2015-69717-P], MICINNMinistry of Science and Innovation, Spain (MICINN) [BFU2017-83317-P], ISCIIIInstituto de Salud Carlos III [PI15/01082, PI16/00851], Career Integration Grant [304111], Ramon y Cajal FellowshipMinistry of Education and Science, Spain [RYC-2011-08391p], MINECO/FEDER [SAF2012-40102], FP7 Marie Curie CIG grant [631035], RETIC [RD16/0008/0014], MetaboHUB project [ANR-11-INBS-0010], FPI contract (MINECO), AGAURAgencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGUAR) [SGR14-297], Fundacion Tatiana Perez de Guzman el Bueno PhD fellowship, European Regional Development Fund (ERDF), a way to build Europe, [SAF2016-77830-R], [RYC-2011-08026], [PI17/00296], and European Project: 221540,EC:FP7:PEOPLE,FP7-PEOPLE-2007-2-1-IEF,PSIEMBL(2009)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Encephalopathy, AMPA receptor, Biochemistry, 03 medical and health sciences, Glutamatergic, 0302 clinical medicine, Internal medicine, Medicine, Missense mutation, Receptor, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, business.industry, Glutamate receptor, Cell Biology, medicine.disease, 3. Good health, Endocrinology, nervous system, biology.protein, NMDA receptor, GRIN2B, business, 030217 neurology & neurosurgery
Abstract

International audience; Autosomal dominant mutations in GRIN2B are associated with severe encephalopathy, but little is known about the pathophysiological outcomes and any potential therapeutic interventions. Genetic studies have described the association between de novo mutations of genes encoding the subunits of the N-methyl-D-aspartate receptor (NMDAR) and severe neurological conditions. Here, we evaluated a missense mutation in GRIN2B, causing a proline-to-threonine switch (P553T) in the GIuN2B subunit of NMDAR, which was found in a 5-year-old patient with Rett-like syndrome with severe encephalopathy. Structural molecular modeling predicted a reduced pore size of the mutant GIuN2B-containing NMDAR5. Electrophysiological recordings in a HEK-293T cell line expressing the mutated subunit confirmed this prediction and showed an associated reduced glutamate affinity. Moreover, GluN2B(P553T)-expressing primary murine hippocampal neurons showed decreased spine density, concomitant with reduced NMDA-evoked currents and impaired NMDAR-dependent insertion of the AMPA receptor subunit GluA1 at stimulated synapses. Furthermore, the naturally occurring coagonist D-serine restored function to GluN2B(P553T)-containing NMDAR5. L-Serine dietary supplementation of the patient was hence initiated, resulting in the increased abundance of D-serine in the plasma and brain. The patient has shown notable improvements in motor and cognitive performance and communication after 11 and 17 months of L-serine dietary supplementation. Our data suggest that L-serine supplementation might ameliorate GRIN2B-related severe encephalopathy and other neurological conditions caused by glutamatergic signaling deficiency.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results