Kinases and phosphatases in neuronal function and dysfunction. PI: Esther Pérez Navarro

Presentation

Our group is interested in the study of molecular mechanisms participating in the control of the voluntary movement and cognitive processes in physiological state, and how they are altered in Huntington's disease in order to identify new therapeutic targets. We have focused on the analysis of the activity of kinases and phosphatases involved in these processes, as well as the pathways they regulate. We are also interested in identifying, at the peripheral level, biomarkers of the neuronal dysfunction that occurs in the brain of Huntington's disease patients. To perform our studies we use mice models of Huntington's disease, in which we analyze behavior by using motor and cognitive tests, and blood, fibroblasts and post-mortem brain samples of control individuals and Huntington’s disease patients.

 

 

Esther Pérez-Navarro
Tenured university lecturer
estherperez@ub.edu

 

Arantxa Golbano
Postdoctoral researcher
arantxa.golbano@ub.edu

 

Carla Castany
Doctoral student
carlacastany@ub.edu

 

Anna Guisado
Doctoral student
annaguisado@ub.edu

 

Lluís Salvador
Undergraduate student
lluissh95@gmail.com

Study of alterations in nuclear lamina and its involvement in the pathophysiology of Huntington’s disease.

Study of protein translation in Huntington’s disease.

Study of the contribution of small RNAs to Huntington’s disease pathogenesis.

Searching of biomarkers in blood and fibroblasts of Huntington’s disease patients.

  • La enfermedad de Huntington como una laminopatía: interacción entre cerebro y la periferia

PI: Esther Pérez Navarro
PID2019-106447RB-I00
Ministerio de Ciencia, Innovación y Universidades
01/06/2020 - 31/05/2023

  • Evaluation of NPT520-34 in the R6/1 transgenic mouse model of Huntington's disease

PI: Esther Pérez Navarro
Neuropore Therapies, Inc
01/09/2018 - 31/07/2019

  • Alteraciones de la lámina nuclear y de la traducción proteica como nuevos mecanismos patogénicos en la enfermedad de Huntington

PI: Esther Pérez Navarro
SAF2016-80573R
Ministerio de Economia y Competitividad (MINECO)
2017 - 2019

  • Optimización y desarrollo de un agente terapéutico basado en ácidos nucleicos para el tratamiento de la enfermedad de Huntington

PI: Esther Pérez Navarro
RTC-2015-3731-1 (RETOS COLABORACION 2015)
Ministerio de Economía y Competitividad (MINECO)
29/09/2015 - 31/12/2017

  • Evaluación de la eficacia de inhibidores epigenéticos en modelos experimentales de patologías humanas

PI: Esther Pérez Navarro
RTC-2015-3898-1 (RETOS COLABORACION 2015)
Ministerio de Economía y Competitividad (MINECO)
29/09/2015 - 31/12/2017

  • Lámina nuclear en la enfermedad de Huntington: Papel en la fisiopatología y aplicaciones terapéuticas
PI: Esther Pérez Navarro
Fundación Ramon Areces

01/01/2015 - 31/12/2017

  • CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CB06/05/0054)

PI: Jordi Alberch Vié
Fondo de Investigaciones Sanitarias. Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación
2007 - 2017

  • RETICS de Terapia Celular (RD06/0010/0006)

PI: Josep M. Canals Coll
Instituto de Salud Carlos III
2007 - 2017

  • Efecto del compuesto PBF999 sobre el déficit motor y cognitivo de ratones R6/1, modelo de la enfermedad de Huntington

PI: Esther Pérez Navarro
Palobiofarma, S.L.
19/05/2014 - 30/09/2014 

  • Regulación de la vía PKA como estrategia terapéutica para la enfermedad de Huntington
PI: Esther Pérez Navarro
Ministerio de Ciencia e Innovación
01/01/2011 - 31/12/2013

For more information for PI publications click in the link:
ORCID
ResearcherID

 

Creus-Muncunill J,* Guisado-Corcoll A,* Venturi V, Pantano L, Escaramís G, García de Herreros M, Solaguren-Beascoa M, Gámez-Valero A, Navarrete C, Masana M, Llorens F, Diaz-Lucena D, Pérez-Navarro E,+ Martí E.+ Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice. Acta Neuropathol. 2021, en premsa doi: 10.1007/ s00401-021- 02272-9. *Co-first autors; +Co-Corresponding authors. PMID: 33547932.

Alcalá-Vida R,* Garcia-Forn M,* Castany-Pladevall C, Creus-Muncunill J, Ito Y, Blanco E, Golbano A, Crespí-Vázquez K, Parry A, Slater G, Samarajiwa S, Peiró S, Di Croce L, Narita M, Pérez-Navarro E. Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease. EMBO Mol Med. 2021 Feb 5;13 (2): e12105. *Co-first autors. PMID: 33369245.

Meneses-Salas E, Garcia-Forn M, Castany-Pladevall C, Lu A, Fajardo A, Jose J, Wahba M, Bosch M, Pol A, Tebar F, Klein AD, Zanlungo S, Pérez-Navarro E, Grewal T, Enrich C, Rentero C. Lack of Annexin A6 Exacerbates Liver Dysfunction and Reduces Lifespan of Niemann-Pick Type C Protein-Deficient Mice. Am J Pathol. 2021 Mar;191 (3): 475-486. doi: 10.1016/ j.ajpath. 2020.12.009. Epub 2020 Dec 17. PMID: 33345999.

Martín-Flores N, Pérez-Sisqués L, Creus-Muncunill J, Masana M, Ginés S, Alberch J, Pérez-Navarro E, Malagelada C. Synaptic RTP801 contributes to motor-learning dysfunction in Huntington's disease. Cell Death Dis. 2020 Jul 30;11(7): 569. doi: 10.1038/ s41419-020- 02775-5. PMID: 32732871.

Creus-Muncunill J, Badillos-Rodríguez R, Garcia-Forn M, Masana M, García-Díaz Barriga G, Guisado-Corcoll A, Alberch J, Malagelada C, Delgado-García JM, Gruart A. Pérez-Navarro E. Increased translation as a novel pathogenic mechanism in Huntington's disease. Brain. 2019 Oct 1; 142(10): 3158-3175. doi: 10.1093/ brain/awz230. PMID: 31365052

Molina-Porcel L, Pérez-Navarro E, García-Forn M, Westaway D, Colom-Cadena M, Gelpi E. Teaching case 3-2019: Are nuclear clefts or invaginations the niche of intranuclear inclusions in FTLD-TDP? Clin Neuropathol. May/Jun 2019; 38(3): 97-99. doi: 10.5414/ NP301202. PMID: 31023421.

Blázquez G, Castañé A, Saavedra A, Masana M, Alberch J, Pérez-Navarro E. Social Memory and Social Patterns Alterations in the Absence of STriatal-Enriched Protein Tyrosine Phosphatase. Front Behav Neurosci, 2019 Jan 25; 12:317. doi: 10.3389/ fnbeh.2018.00317. eCollection 2018. PMID: 30760987.

Saavedra A, Ballesteros JJ, Tyebji S, Martínez-Torres S, Blázquez G, López-Hidalgo R, Azkona G, Alberch J, Martín ED, Pérez-Navarro E. Proteolytic Degradation of Hippocampal STEP(61) in LTP and Learning. Mol Neurobiol. 2018, en premsa (doi: 10.1007/s12035-018-1170-1)

García-Forn M, Martínez-Torres S, García-Díaz Barriga G, Alberch J, Milà M, Azkona G, Pérez-Navarro E. Pharmacogenetic modulation of STEP improves motor and cognitive function in a mouse model of Huntington's disease. Neurobiol Dis. 2018, 20:88-97

Saavedra A, García-Díaz Barriga G, Pérez-Navarro E, Alberch J. Huntington's disease: novel therapeutic perspectives hanging in the balance. Expert Opin Ther Targets. 2018, 22:385-399

Creus-Muncunill J, Rué L, Alcalá-Vida R, Badillos-Rodríguez R, Romaní-Aumedes J, Marco S, Alberch J, Perez-Otaño I, Malagelada C, Pérez-Navarro E. Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration. Mol Neurobiol. 2018, 55:7728-7742

Cases S, Saavedra A, Tyebji S, Giralt A, Alberch J, Pérez-Navarro E. Age-related changes in STriatal-Enriched protein tyrosine Phosphatase levels: Regulation by BDNF. Mol Cell Neurosci. 2018; 86:41-49

Giralt A, Gómez-Climent MÁ, Alcalá R, Bretin S, Bertrand D, Delgado-García JM, Pérez-Navarro E, Alberch J, Gruart A. The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3-CA1 long-term potentiation and structural synaptic changes in old mice. Neuropharmacology. 2017, in press; PMID: 28603025.

Saavedra A, Fernández-García S, Cases S, Puigdellívol M, Alcalá-Vida R, Martín-Flores N, Alberch J, Ginés S, Malagelada C, Pérez-Navarro E. Chelerythrine promotes Ca(2+)-dependent calpain activation in neuronal cells in a PKC-independent manner. Biochim Biophys Acta. 2017 Apr;1861(4):922-935

Lao-Peregrín C, Ballesteros JJ, Fernández M, Zamora-Moratalla A, Saavedra A, Gómez Lázaro M, Pérez-Navarro E, Burks D, Martín ED. Caffeine-mediated BDNF release regulates long-term synaptic plasticity through activation of IRS2 signaling. Addict Biol. 2016, in press; PMID: 27457910.

Rué L, Bañez-Coronel M, Creus-Muncunill J, Giralt A, Alcalá-Vida R, Mentxaka G, Kagerbauer B, Zomeño-Abellán MT, Aranda Z, Venturi V, Pérez-Navarro E, Estivill X, Martí E. Targeting CAG repeat RNAs reduces Huntington's disease phenotype independently of huntingtin levels. J Clin Invest. 2016, 126:4319-4330.

Puigdellívol M, Saavedra A, Pérez-Navarro E. Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF. Brain Pathol. 2016, 26:752-771.

Bosch M, Fajardo A, Alcalá-Vida R, Fernández-Vidal A, tebar F, Enrich C, Cardellach F, Pérez-Navarro E, Pol A. Hepatic primary and secondary cholesterol deposition and damage in Niemann-Pick Disease. Am J Pathol., 2016, 186:517-523

Xu J, Kurup P, Azkona G, Baguley TD, Saavedra A, Nairn AC, Ellman JA, Pérez-Navarro E, Lombroso PJ. Down-regulation of BDNF in cell and animal models increases striatal-enriched protein tyrosine phosphatase 61 (STEP(61)) levels. J Neurochem, 2016, 136:285-294

Azkona G, Saavedra A, Aira Z, Aluja D, Xifró X, Baguley T, Alberch J, Ellman JA, Lombroso PJ, Azkue JJ, Pérez-Navarro E. STEP modulates nociception: evidences from genetic deletion and pharmacological inhibition. Pain, 2016, 157:377-386

Saavedra A, Puigdellívol M, Tyebji S, Kurup P, Xu J, Ginés S, Alberch J, Lombroso PJ, Pérez-Navarro E. BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome. Mol Neurobiol, 2016, 53:4261-4273

Martín-Flores N, Romaní-Aumedes J, Rué L, Canal M, Sanders P, Straccia M, Allen ND, Alberch J, Canals JM, Pérez-Navarro E,* Malagelada C*. RTP801 Is Involved in Mutant Huntingtin-Induced Cell Death. Mol Neurobiol. 2016, 53:2857-2868. *Corresponding authors

Fernández-Nogales M, Hernández F, Miguez A, Alberch J, Ginés S, Pérez-Navarro E, Lucas JJ. Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease. Hum Mol Genet, 2015, 24:5040-5052

Tyebji S, Saavedra A, Canas PM, Pliassova A, Delgado-García JM, Alberch J, Cunha RA, Gruart A, Pérez-Navarro E. Hyperactivation of D1 and A2A receptors contributes to cognitive dysfunction in Huntington's disease. Neurobiol Dis, 2015, 74:41-57

Azkona G, López de Maturana R, Marcilla I, Sousa A, Pérez-Navarro E, Luquin MR, Sánchez-Pernaute R. Sustained increase of PKA activity in the post-commissural putamen of dyskinetic monkeys. Mol Neurobiol, 2014, 50:1131-1141.

Azkona G, Sagarduy A, Aristieta A, Vazquez N, Zubillaga V, Ruíz-Ortega JA, Pérez-Navarro E, Ugedo L, Sánchez-Pernaute R. Buspirone anti-dyskinetic effect is correlated with temporal normalization of dysregulated striatal DRD1 signalling in L-DOPA-treated rats. Neuropharmacology. 2014 79:726-737

Rué L, Alcalá-Vida R, López-Soop G, Creus-Muncunill J, Alberch J, Pérez-Navarro E. Early Down-Regulation of PKCδ as a Pro-Survival Mechanism in Huntington's Disease. Neuromolecular Med. 2014 16:25-37

Saavedra A, Giralt A, Arumí H, Alberch J, Pérez-Navarro E. Regulation of hippocampal cGMP levels as a candidate to treat cognitive deficits in Huntington's disease. PLoS One. 2013 8:e73664.

Pascual-García M, Rué L, León T, Julve J, Carbó JM, Matalonga J, Auer H, Celada A, Escolà-Gil JC, Steffensen KR, Pérez-Navarro E, Valledor AF. Reciprocal negative cross-talk between liver X receptors (LXRs) and STAT1: effects on IFN-γ-induced inflammatory responses and LXR-dependent gene expression. J Immunol., 2013, 190:6520-32.

Giralt A, Saavedra A, Carretón O, Arumí H, Tyebji S, Alberch J, Pérez-Navarro E. PDE10 inhibition increases GluA1 and CREB phosphorylation and improves spatial and recognition memories in a Huntington's disease mouse model. Hippocampus 2013 23:684-95

Villar-Menéndez I, Blanch M, Tyebji S, Pereira-Veiga T, Albasanz JL, Martín M, Ferrer I, Pérez-Navarro E, Barrachina M. Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington's disease. Neuromolecular Med, 2013 15:295-309.

Rué L, Lopez-Soop G, Gelpí E, Martínez-Vicente M, Alberch J, Pérez-Navarro E. Brain region- and age-dependent dysregulation of p62 and NBR1 in a mouse model of Huntington’s disease. Neurobiol Dis, 2013 52:219-28.

Giralt A, Saavedra S, Alberch J, Pérez-Navarro E. Cognitive dysfunction in Huntington’s disease: Humans, mouse models and molecular mechanisms. J Huntington’s Dis. 2012, 1:155-173 (DOI 10.3233). Review

Anglada-Huguet M, Giralt A, Pérez-Navarro E, Alberch J, Xifró X. Activation of Elk‐1 participates as a neuroprotective compensatory mechanism in models of Huntington’s disease. J Neurochem. 2012, 121:639-648

Xifró X, Anglada-Huguet M, Rué L, Saavedra A, Pérez-Navarro E, Alberch J. Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity. Mol Neurodegener. 2011, 6:74

Giralt A, Saavedra A, Carretón O, Xifró X, Alberch J, Pérez-Navarro E. Increased PKA signaling disrupts recognition memory and spatial memory: role in Huntington’s disease. Hum. Mol. Genet. 2011, 20:4232-4247. For this work Albert Giralt has been awarded with the prize “Young investigator of the year” granted by CIBERNED, December 2012.

Saavedra A, Giralt A, Rué L, Xifró X, Xu J, Ortega Z, Lucas JJ, Lombroso PJ, Alberch J, Pérez-Navarro E. Striatal-Enriched protein tyrosine Phosphatase expression and activity in Huntington’s disease – a STEP in the resistance to excitotoxicity. J Neurosci. 2011, 31:8150-8162

Bosch M, Marí M, Herms A, Fernández A, Fajardo A, Kassan A, Giralt A., Colell A, Balgoma D, Barbero E, González-Moreno E, Matias N, Tebar F, Balsinde J, Camps M, Enrich C, Gross SP, García-Ruiz C, Pérez-Navarro E, Fernández-Checa JC,* Pol A*. Caveolin-1 deficiency causes cholesterol dependent mitochondrial dysfunction and apoptotic susceptibility. Curr Biol. 2011, 21:681-621. *Corresponding authors. Editor’s Choice, Science, 2011, 332:1129

Sánchez-Gómez MV, Alberdi E, Pérez-Navarro E, Alberch J, Matute C. Bax and calpain mediate excitotoxic oligodendrocyte death induced by activation of both AMPA and kainate receptors. J Neurosci. 2011, 31: 2996-3006

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