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Lab 15 – Neurobioquímica

Our work mainly focuses on the role of glial cells in health and disease.
We study the cellular and molecular bases underlying important CNS pathologies in which astrocytes play an essential role.
We are interested in gap junctions and connexins, their molecular constituents. We showed that Src is involved in the molecular mechanism by which connexin43 reduces cell proliferation and glucose uptake. Based on this mechanism we have designed a cell-penetrating peptide (TAT-Cx43266-283) with important antitumor effects in glioma models, in vitro and in vivo. We are currently focussed on the translation of this knowledge into the clinic and investigating the cellular and molecular mechanism involved in the progression of malignant brain tumours.

Investigador principal del grupo

Dra. Mª Aránzazu Tabernero Urbieta
Catedrática de Universidad
Producción Científica

Dr. José M Medina Jiménez
(Emeritus Professor)

María Paniagua Sancho
(Postdoctoral Research)

Laura García Vicente
(Predoctoral Research; FPU)

Andrea Álvarez Vázquez
(Predoctoral Research; JCyL)

Raquel Flores Hernández
(Predoctoral Research; JCyL)

Pilar Cerveró García
(Predoctoral Research; JCyL)

  1. Sara G. Pelaz, Claudia Ollauri-Ibáñez, Concepción Lillo, and Arantxa Tabernero. Impairment of autophagic flux participates in the antitumor effects of TAT-Cx43266-283 in glioblastoma stem cells. Cancers 2021, 13, 4262.

https://www.mdpi.com/2072-6694/13/17/4262

  1. Sara G. Pelaz, Myriam Jaraíz-Rodríguez, Andrea Álvarez Vázquez, Rocío Talaverón, Laura García-Vicente, Raquel Flores Hernández, Marta Gómez de Cedrón, María Tabernero, Ana Ramírez de Molina, Concepción Lillo, José M. Medina, and Arantxa Tabernero. Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283EBioMedicine (published by the Lancet). Volume 62, December 2020, 103134. https://doi.org/10.1016/j.ebiom.2020.103134 .

https://www.sciencedirect.com/science/article/pii/S2352396420305107?via%3Dihub

  1. R. Talaverón, E.R. Matarredona, A. Herrera, J.M. Medina and A. Tabernero. Connexin43 region 266-283, via Src inhibition, reduces neural progenitor cell proliferation promoted by EGF and FGF-2 and increases astrocytic differentiation. Int. J. Mol. Sci. 2020, 21, 8852; doi:10.3390/ijms21228852.

https://pubmed.ncbi.nlm.nih.gov/33238452/

  1. Tabernero A, Koulakoff A, Roux L, Venance L, Leybaert L, Sáez JC, Naus CC. Christian Giaume (November 1951-July 2019). Glia. 2020 Jul;68(7):1321-1328. https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23836
  2. Jaraíz-Rodríguez M, Talaverón R, García-Vicente L, Pelaz SG, Domínguez-Prieto M, Álvarez-Vázquez A, Flores-Hernández R, Sin WC, Bechberger J, Medina JM, Naus CC, Tabernero A. (2020) Connexin43 peptide, TAT-Cx43266-283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo. Neuro-Oncology. Apr 15;22(4):493-504. https://academic.oup.com/neuro-oncology/article/22/4/493/5688710
  3.  Trond Aasen, Edward Leithe, Sheila Graham, Petra Kameritsch, María Mayán, Marc Mesnil, Kristin Pogoda and Arantxa Tabernero. (2019) Connexins in Cancer: Bridging the Gap to the Clinic. Oncogene. Jun;38(23):4429-4451. https://pubmed.ncbi.nlm.nih.gov/30814684/
  4.  Domínguez-Prieto M, Velasco A, Tabernero A, Medina JM. (2018) Endocytosis and Transcytosis of Amyloid-β Peptides by Astrocytes: A Possible Mechanism for Amyloid-β Clearance in Alzheimer’s Disease. J Alzheimers Dis. 

https://pubmed.ncbi.nlm.nih.gov/30103329/

  1. Ester Gangoso, Rocio Talaverón, Myriam Jaraíz-Rodríguez, Marta Domínguez-Prieto, Pascal Ezan, Anette Koulakoff, Jose M Medina, Christian Giaume and Arantxa Tabernero (2017) A c-Src inhibitor peptide based on Connexin43 exerts neuroprotective effects through the inhibition of glial hemichannel activity. Frontiers in Molecular Neuroscience. 10:418. https://pubmed.ncbi.nlm.nih.gov/29326548/
  2. Myriam Jaraíz-Rodríguez, Mª Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina and Arantxa Tabernero (2017) A short region of connexin43 reduces human glioma stem cell migration, invasion and survival through Src, PTEN and FAK. Stem Cell Reports. 9:451-463. https://pubmed.ncbi.nlm.nih.gov/28712848/
  3. Domínguez-Prieto M, Velasco A, Vega L, Tabernero A, Medina JM. (2017) Aberrant Co-localization of Synaptic Proteins Promoted by Alzheimer’s Disease Amyloid-β Peptides: Protective Effect of Human Serum Albumin. J Alzheimers Dis. 55:171-182.
  4. Ana González-Sánchez, Myriam Jaraíz-Rodríguez, Marta Domínguez-Prieto, Sandra Herrero-González, Jose M Medina y Arantxa Tabernero. (2016) Connexin43 recruits PTEN and CSK to inhibit c-Src in glioma cells and astrocytes. Oncotarget 7: 49819-49833. doi: 10.18632/oncotarget. 10454. https://pubmed.ncbi.nlm.nih.gov/27391443/
  5. Arantxa Tabernero, Ester Gangoso, Myriam Jaraíz-Rodríguez and Jose M Medina. (2016) The role of connexin43-Src interaction in astrocytomas: a molecular puzzle. Neuroscience 323:183-94. https://pubmed.ncbi.nlm.nih.gov/25711938/
  6. Ester Gangoso, Cécile Thirant, Hervé Chneiweiss, Jose M Medina and Arantxa Tabernero. (2014) A cell-penetrating peptide based on the interaction between c-Src and connexin43 reverses glioma stem cell phenotype. Cell Death and Disease. 5, e1023; doi:10.1038/cddis.2013.560. https://pubmed.ncbi.nlm.nih.gov/24457967/
  7. Sandra Herrero-González, Ester Gangoso, Christian Giaume, Christian C. Naus, Jose M Medina and Arantxa Tabernero. (2010) “Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells”. Oncogene. 29: 5712–5723.https://pubmed.ncbi.nlm.nih.gov/20676131/
  1. Aproximación multidisciplinar para el estudio del mecanismo de acción y optimización de péptidos antitumorales basados en la conexina-43 en modelos de glioma in vitro e in vivo. Consejería de Educación y Cultura. Junta de Castilla y León. FEDER. I.P.: Aránzazu Tabernero Urbieta. Ref: SA125P20 (6-11-2020/5-11-23).
  2. Research netwok: “Red de péptidos en biomedicina y nanociencia”, convocatoria Acciones de dinamización «Redes de Investigación» (Programa Estatal de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+I). ref: RED2018-102417-T. (1-1-2020/31-12-2022). I.P.: Eugenio Vázquez Sentis.
  3. Contribución de los astrocitos y la microglía a los efectos antitumorales de péptidos basados en la conexina43 usando modelos de glioma in vitro e in vivo. Ministerio de Ciencia, Innovación y Universidades. Ref: RTI2018-099873-B-I00. (1-1-2019/31-12-2021). I.P.: A. Tabernero.