MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.This work was supported by Carlos III Institute, (PI17/00189 and DTS15/00069), by Fondo Europeo de Desarrollo Regional—FEDER, by the Gipuzkoa Regional Council (DFG 15/006), by grant from the Basque Government (RIS3/DTS/2018222025), by the Department of Industry of the Basque Country (ELKARTEK 16/014), and the Spanish State Research Agency (SAF2017-87670-R) and Maria de Maeztu Units of Excellence Program Grant MDM-2017-0720). I.O.-Q., A.A. and L.I. were supported by the Department of Education of the Basque Government. IOQ and LAN were supported by EMBO short Term Fellowship Programme. LAN was supported by a Canadian graduate scholarship from the Canadian Institutes of Health Research (CGS-D CIHR).PRC was supported by Ikerbasque, the Basque Foundation for Science

The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version Human Molecular Genetics 2006 15(23):3436-3445. is available online at: http://hmg.oxfordjournals.org/cgi/content/full/15/23/3436Autosomal dominant lateral temporal epilepsy (ADTLE) is a partial epilepsy caused by mutations in LGI1, a multidomain protein of unknown function. To begin to understand the biological function of LGI1, we have determined its pattern of glycosylation, subcellular expression and capacity for secretion. LGI1 is expressed as two different isoforms in the brain, and we show that the long isoform is a secreted protein, whereas the short isoform is retained in an intracellular pool. ADLTE-related mutants of the long form are defective for secretion and are retained in the endoplasmic reticulum and Golgi complex. Finally, we show that normal secreted LGI1 specifically binds to the cell surface of differentiated PC12 cells. We propose that LGI1 is a secreted factor important for neuronal development and that ADTLE is a disease that results from the loss of regulation in the protein available either extracellular or intracellularly.This work was supported by grants from the Ministerio de Educación y Ciencia (SAF2002-00060 and SAF2005-00136) to J.P.T. and from the Canadian Institute of Heath Research (PPP147918) to P.A.B. S.S.P. is funded by a fellowship of the Generalitat Valenciana (CTBPRB/2002/35), J.M.M.R. is funded by an FPU and a Bancaixa fellowship. Support from the Ministerio de Educación y Ciencia (BES-2003-0243, to A.A.I.) and from the Ministerio de Sanidad y Consumo (BF03/00182, to V.H.P.) is also acknowledged. K.F. is funded by a Canadian NSERC award.Peer reviewe

MiR-219a-5p enriched extracellular vesicles induce OPC differentiation and EAE improvement more efficiently than liposomes and polymeric nanoparticles

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

none22noneAyerdi-Izquierdo A.; Stavrides G.; Selles-Martinez J.J.; Larrea L.; Bovo G.; Lopez de Munain A.; Bisulli F.; Marti-Masso J.F.; Michelucci R.; Poza J.J.; Tinuper P.; Stephani U.; Striano P.; Striano S.; Staub E.; Sarafidou T.; Hinzmann B.; Moschonas N.; Siebert R.; Deloukas P.; Nobile C.; Perez-Tur J.Ayerdi-Izquierdo A.; Stavrides G.; Selles-Martinez J.J.; Larrea L.; Bovo G.; Lopez de Munain A.; Bisulli F.; Marti-Masso J.F.; Michelucci R.; Poza J.J.; Tinuper P.; Stephani U.; Striano P.; Striano S.; Staub E.; Sarafidou T.; Hinzmann B.; Moschonas N.; Siebert R.; Deloukas P.; Nobile C.; Perez-Tur J

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

The definitive version is available at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T34-4JYTRWV-1&_user=4221266&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000048559&_version=1&_urlVersion=0&_userid=4221266&md5=efd2685823995c3ad94101782def140bMutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.This work is funded by a grant from the Ministerio de Educación y Ciencia (SAF2002-00060) to JP-T, from the Ilundain Fundazioa to ALdM, JJP and JFMM, from Telethon-Italy (GGP02339) to CN and RM, and from the Commissione Genetica, Lega Italiana Contro l’Epilessia (LICE) to RM and CN. JP-T and CN are recipients of a collaborative CSIC-CNR grant (2003IT0018). JP-T is part of the Grupos de Excelencia of the Generalitat Valenciana (GRUPOS03/015).Peer reviewe

Métodos de innovación docente aplicados a los estudios de Ciencias de la Comunicación

Se analiza el fenómeno de la implantación del Espacio Europeo de Educación Superior (EEES) a los estudios de Ciencias de la Comunicación, desde el punto de vista del profesorado. En este sentido se analizan experiencias educativas como: cuadernos de visionado para la iniciación de los alumnos en el comentario fílmico; la utilización didáctica de recursos audiovisuales; el uso de películas como herramientas en la educación de estudiantes; el uso de la televisión informativa; y la aplicación de técnicas de aprendizaje colaborativo entre otras propuestas. Asimismo, se estudia el estado de implantación del EEES en España y se describen propuestas de aplicación del mismo a diferentes áreas de los estudios de Ciencias de la Comunicación. También se dedican estudios a la descripción de nuevas estrategias docentes en el marco del EEES y se proponen fórmulas de evaluación de los aprendizajes. Por último se presta atención a la aplicación de las Tecnologías de la Información y la Comunicación a los citados estudios y se definen nuevas herramientas para apoyar a los estudiantes en su labor.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]