Lineas de Investigación

01. Neuroinflamación y respuesta glial en la enfermedad de Alzheimer.

02. Descifrar nuevos mecanismos (enfoques) patogénicos implicados en la enfermedad de Alzheimer que permitan un mayor éxito traslacional a la clínica humana. Identificación de biomarcadores y dianas terapéuticas.

03. Desarrollo de nuevos modelos animales de la enfermedad de Alzheimer que recapitulen mejor la patología de los pacientes. Estudios preclínicos de nuevas estrategias terapéuticas.

04. Desarrollo de modelos in vitro de la enfermedad de Alzheimer mediante el empleo de células iPSCs derivadas de pacientes. Estudios de mecanismos patogénicos y evaluación de nuevos fármacos.

Image Description


Proyectos de Investigación

Disfunción glial en la enfermedad de Alzheimer: implicaciones patogénicas y potencial clínico Proyecto Colaborativo CIBERNED

Universidad de Málaga
. 2018

PI18/01557. Descifrando la diversidad funcional de la respuesta microglial y astroglial en la enfermedad de Alzheimer: potencial patológico y terapéutico

INSTITUTO DE SALUD CARLOS III
. 2019

Desregulación del Sistema immune innato cerebral y la enfermedad de Alzheimer: nuevas dianas para futuras terapias.

Junta de Andalucía
. 2018

PI-0276-2018 Inmunidad Innata Cerebral y Periférica en la Enfermedad de Alzheimer: Disección Molecular de Nuevas Vías Patogénicas y Potencial Terapéutico

CONSEJERÍA DE SALUD
PROYECTOS DE INVESTIGACIÓN EN SALUD 2018

Publicaciones científicas

  • Todo
  • D1
  • Q1
  • Q2
  • Otro
Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer’s disease.

Baglietto-Vargas D, Sánchez-Mejias E, Navarro V, Jimenez S, Trujillo-Estrada L, Gómez-Arboledas A, Sánchez-Mico M, Sánchez-Varo R, Vizuete M, Dávila JC, García-Verdugo JM, Vitorica J, Gutierrez A.
Sci Rep. 2017 Aug 30;7(1):10085.

Alzheimer’s disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer’s patients. In this regard, new evidence linking Alzheimer’s disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlyi […]

Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity.

Peñalver A, Campos-Sandoval JA, Blanco E, Cardona C, Castilla L, Martín-Rufián M, Estivill-Torrús G, Sánchez-Varo R, Alonso FJ, Pérez-Hernández M, Colado MI, Gutiérrez A, de Fonseca FR, Márquez J.
Front Mol Neurosci. 2017 Sep 5;10:278.

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encod […]

N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson’s disease.

García-Sanz P, Orgaz L, Bueno-Gil G, Espadas I, Rodríguez-Traver E, Kulisevsky J, Gutierrez A, Dávila JC, González-Polo RA, Fuentes JM, Mir P, Vicario C, Moratalla R.
Mov Disord. 2017 Oct;32(10):1409-1422.

Heterozygous mutations in the GBA1 gene, which encodes the lysosomal enzyme β-glucocerebrosidase-1, increase the risk of developing Parkinson’s disease, although the underlying mechanisms remain unclear. The aim of this study was to explore the impact of the N370S-GBA1 mutation on cellular homeostasis and vulnerability in a patient-specific cellular model of PD. […]

Amyloid-beta impairs TOM1-mediated IL-1R1 signaling.

Cadete Martini A, Gomez-Arboledas A, Forner S, Rodriguez-Ortiz CJ, McQuade A, Danhash E, Phan J, Javonillo D, Ha JV, Tram M, Trujillo-Estrada L, da Cunha C, Ager RR, Davila JC, Kitazawa M, Blurton-Jones M, Gutierrez A, Baglietto-Vargas D, Medeiros R, LaFerla FM.
Proc Natl Acad Sci U S A. 2019 Sep 30.

Defects in interleukin-1β (IL-1β)-mediated cellular responses contribute to Alzheimer’s disease (AD). To decipher the mechanism associated with its pathogenesis, we investigated the molecular events associated with the termination of IL-1β inflammatory responses by focusing on the role played by the target of Myb1 (TOM1), a negative regulator of the interleukin-1β receptor-1 (IL-1R1). We first show that TOM1 steady-state levels are reduced in […]

Astrocytes: From the Physiology to the Disease.

Trujillo-Estrada L, Gomez-Arboledas A, Forner S, Martini AC, Gutierrez A, Baglietto-Vargas D, La Ferla FM.
Curr Alzheimer Res. 2019 Aug 30.

Astrocytes are key cells for adequate brain formation and regulation of cerebral blood flow as well as for the maintenance of neuronal metabolism, neurotransmitter synthesis and exocytosis, and synaptic transmission. Many of these functions are intrinsically related to neurodegeneration, allowing refocusing on the role of astrocytes in physiological and neurodegenerative states. Indeed, emerging evi- dence in the field indicates that abnormalitie […]

Use of human pluripotent stem cell-derived cells for neurodegenerative disease modeling and drug screening platform.

Garcia-Leon JA, Vitorica J, Gutierrez A.
Future Med Chem. 2019 Jun;11(11):1305-1322.

Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This fact, together with the lack of reliable disease models, has precluded the development of effective therapies counteracting the disease progression. The advent of human pluripotent stem cells has revolutionized the field allowing the generation of disease-relevant neural cell types that can be used for disease modeling, drug screening and, p […]

Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease.

Boza-Serrano A, Ruiz R, Sanchez-Varo R, García-Revilla J, Yang Y, Jimenez-Ferrer I, Paulus A, Wennström M, Vilalta A, Allendorf D, Davila JC, Stegmayr J, Jiménez S, Roca-Ceballos MA, Navarro-Garrido V, Swanberg M, Hsieh CL, Real LM, Englund E, Linse S, Leffler H, Nilsson UJ, Brown GC, Gutierrez A, Vitorica J, Venero JL, Deierborg T.
Acta Neuropathol. 2019 Aug;138(2):251-273.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brain […]

Distinct disease-sensitive GABAergic neurons in the perirhinal cortex of Alzheimer’s mice and patients.

Sanchez-Mejias E, Nuñez-Diaz C, Sanchez-Varo R, Gomez-Arboledas A, Garcia-Leon JA, Fernandez-Valenzuela JJ, Mejias-Ortega M, Trujillo-Estrada L, Baglietto-Vargas D, Moreno-Gonzalez I, Davila JC, Vitorica J, Gutierrez A.
Brain Pathol. 2019 Sep 6.

Neuronal loss is the best neuropathological substrate that correlates with cortical atrophy and dementia in Alzheimer’s disease (AD). Defective GABAergic neuronal functions may lead to cortical network hyperactivity and aberrant neuronal oscillations and in consequence, generate a detrimental alteration in memory processes. In this study, using immunohistochemical and stereological approaches, we report that the two major and non-overlapping grou […]


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