Full Text Journal Articles by
Author Javier Vitorica

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Animal and Cellular Models of Alzheimer's Disease: Progress, Promise, and Future Approaches.

Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nuñez-Diaz, Jose Carlos Davila, Javier Vitorica, Frank M LaFerla, Ines Moreno-Gonzalez, Antonia Gutierrez, David Baglietto-Vargas,

Alzheimer's disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease ... Read more >>

Neuroscientist (The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry)
[2021, :10738584211001753]

Cited: 0 times

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Reactive astrocyte nomenclature, definitions, and future directions.

Carole Escartin, Elena Galea, András Lakatos, James P O'Callaghan, Gabor C Petzold, Alberto Serrano-Pozo, Christian Steinhäuser, Andrea Volterra, Giorgio Carmignoto, Amit Agarwal, Nicola J Allen, Alfonso Araque, Luis Barbeito, Ari Barzilai, Dwight E Bergles, Gilles Bonvento, Arthur M Butt, Wei-Ting Chen, Martine Cohen-Salmon, Colm Cunningham, Benjamin Deneen, Bart De Strooper, Blanca Díaz-Castro, Cinthia Farina, Marc Freeman, Vittorio Gallo, James E Goldman, Steven A Goldman, Magdalena Götz, Antonia Gutiérrez, Philip G Haydon, Dieter H Heiland, Elly M Hol, Matthew G Holt, Masamitsu Iino, Ksenia V Kastanenka, Helmut Kettenmann, Baljit S Khakh, Schuichi Koizumi, C Justin Lee, Shane A Liddelow, Brian A MacVicar, Pierre Magistretti, Albee Messing, Anusha Mishra, Anna V Molofsky, Keith K Murai, Christopher M Norris, Seiji Okada, Stéphane H R Oliet, João F Oliveira, Aude Panatier, Vladimir Parpura, Marcela Pekna, Milos Pekny, Luc Pellerin, Gertrudis Perea, Beatriz G Pérez-Nievas, Frank W Pfrieger, Kira E Poskanzer, Francisco J Quintana, Richard M Ransohoff, Miriam Riquelme-Perez, Stefanie Robel, Christine R Rose, Jeffrey D Rothstein, Nathalie Rouach, David H Rowitch, Alexey Semyanov, Swetlana Sirko, Harald Sontheimer, Raymond A Swanson, Javier Vitorica, Ina-Beate Wanner, Levi B Wood, Jiaqian Wu, Binhai Zheng, Eduardo R Zimmer, Robert Zorec, Michael V Sofroniew, Alexei Verkhratsky,

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear ... Read more >>

Nat Neurosci (Nature neuroscience)
[2021, 24(3):312-325]

Cited: 41 times

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Amyloid-β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease.

Maria V Sanchez-Mico, Sebastian Jimenez, Angela Gomez-Arboledas, Clara Muñoz-Castro, Carmen Romero-Molina, Victoria Navarro, Elisabeth Sanchez-Mejias, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Elena Galea, José C Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid-β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced ... Read more >>

Glia (Glia)
[2021, 69(4):997-1011]

Cited: 2 times

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Human Pluripotent Stem Cell-Derived Neural Cells as a Relevant Platform for Drug Screening in Alzheimer's Disease.

Juan Antonio Garcia-Leon, Laura Caceres-Palomo, Elisabeth Sanchez-Mejias, Marina Mejias-Ortega, Cristina Nuñez-Diaz, Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez,

Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tangles are prime features of Alzheimer's disease (AD). The pathology of AD is very complex and still not fully understood, since different neural cell types are involved in the disease. Although neuronal function is clearly deteriorated in AD patients, recently, an increasing number ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2020, 21(18):]

Cited: 4 times

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Enhancing microtubule stabilization rescues cognitive deficits and ameliorates pathological phenotype in an amyloidogenic Alzheimer's disease model.

Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Clara Muñoz-Castro, Vanessa De Castro, Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Cristina Nuñez-Diaz, Angela Gomez-Arboledas, Ines Moreno-Gonzalez, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez,

In Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):14776]

Cited: 0 times

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Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells.

María García-Bonilla, Betsaida Ojeda-Pérez, María L García-Martín, M Carmen Muñoz-Hernández, Javier Vitorica, Sebastián Jiménez, Manuel Cifuentes, Leonor Santos-Ruíz, Kirill Shumilov, Silvia Claros, Antonia Gutiérrez, Patricia Páez-González, Antonio J Jiménez,

<h4>Background</h4>In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been ... Read more >>

Stem Cell Res Ther (Stem cell research & therapy)
[2020, 11(1):121]

Cited: 1 time

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

Juan Antonio Garcia-Leon, Javier Vitorica, Antonia Gutierrez,

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 ... Read more >>

Future Med Chem (Future medicinal chemistry)
[2019, 11(11):1305-1322]

Cited: 6 times

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

Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Juan García-Revilla, Yiyi Yang, Itzia Jimenez-Ferrer, Agnes Paulus, Malin Wennström, Anna Vilalta, David Allendorf, Jose Carlos Davila, John Stegmayr, Sebastian Jiménez, Maria A Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine L Hsieh, Luis M Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf J Nilsson, Guy C Brown, Antonia Gutierrez, Javier Vitorica, Jose Luis Venero, Tomas Deierborg,

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 ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2019, 138(2):251-273]

Cited: 32 times

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Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

Mercedes Pérez-Jiménez, Paula Sansigre, Amador Valladares, Mónica Venegas-Calerón, Alicia Sánchez-García, José Monje, Sara Esteban-García, Irene Suarez-Pereira, Javier Vitorica, José Ríos, Marta Artal-Sanz, Ángel Carrión, Manuel Muñoz,

Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity by a still not fully understood mechanism. We find that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones and increases longevity. This increased ... Read more >>

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Galectin-3, A Novel Endogenous Trem2 Ligand, Regulates Inflammatory Response and Aβ Fibrilation in Alzheimer’s Disease

Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Yiyi Yang, Juan García-Revilla, Itzia Jimenez-Ferrer, Agnes Paulus, Malin Wennström, Anna Vilalta, David Allendorf, Jose Carlos Davila, Christopher Dunning, John Stegmayr, Sebastian Jiménez, Maria Angustias Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine Hsieh, Luis Miguel-Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf Nilsson, Antonia Gutierrez, Guy Brown, Javier Vitorica, Jose Luis Venero, Tomas Deierborg, ,

<h4>ABSTRACT</h4> Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, intraneuronal tau neurofibrillary tangles 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 ... Read more >>

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Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology.

Carmen Romero-Molina, Victoria Navarro, Raquel Sanchez-Varo, Sebastian Jimenez, Juan J Fernandez-Valenzuela, Maria V Sanchez-Mico, Clara Muñoz-Castro, Antonia Gutierrez, Javier Vitorica, Marisa Vizuete,

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau ... Read more >>

Front Cell Neurosci (Frontiers in cellular neuroscience)
[2018, 12:421]

Cited: 5 times

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Microglia in Alzheimer's Disease: Activated, Dysfunctional or Degenerative.

Victoria Navarro, Elisabeth Sanchez-Mejias, Sebastian Jimenez, Clara Muñoz-Castro, Raquel Sanchez-Varo, Jose C Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, ... Read more >>

Front Aging Neurosci (Frontiers in aging neuroscience)
[2018, 10:140]

Cited: 37 times

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Toward a New Concept of Alzheimer's Disease Models: A Perspective from Neuroinflammation.

Antonia Gutierrez, Javier Vitorica,

The continuing failure to develop an effective treatment for Alzheimer's disease urges a better understanding of the pathogenic mechanisms and the improvement of current animal models to facilitate success for clinical interventions. The transgenic models have been so far designed to recapitulate one, or both, protein lesions found in the ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2018, 64(s1):S329-S338]

Cited: 11 times

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Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease.

Angela Gomez-Arboledas, Jose C Davila, Elisabeth Sanchez-Mejias, Victoria Navarro, Cristina Nuñez-Diaz, Raquel Sanchez-Varo, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Juan Jose Fernandez-Valenzuela, Marisa Vizuete, Joan X Comella, Elena Galea, Javier Vitorica, Antonia Gutierrez,

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this ... Read more >>

Glia (Glia)
[2018, 66(3):637-653]

Cited: 46 times

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Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer's disease.

David Baglietto-Vargas, Elisabeth Sánchez-Mejias, Victoria Navarro, Sebastián Jimenez, Laura Trujillo-Estrada, Angela Gómez-Arboledas, Maria Sánchez-Mico, Raquel Sánchez-Varo, Marisa Vizuete, José Carlos Dávila, José Manuel García-Verdugo, Javier Vitorica, Antonia Gutierrez,

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 ... Read more >>

Sci Rep (Scientific reports)
[2017, 7(1):10085]

Cited: 11 times

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Acute and Chronic Sustained Hypoxia Do Not Substantially Regulate Amyloid-β Peptide Generation In Vivo.

Alberto Serrano-Pozo, Manuel A Sánchez-García, Antonio Heras-Garvín, Rosana March-Díaz, Victoria Navarro, Marisa Vizuete, José López-Barneo, Javier Vitorica, Alberto Pascual,

<h4>Background</h4>Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex ... Read more >>

PLoS One (PloS one)
[2017, 12(1):e0170345]

Cited: 1 time

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Soluble phospho-tau from Alzheimer's disease hippocampus drives microglial degeneration.

Elisabeth Sanchez-Mejias, Victoria Navarro, Sebastian Jimenez, Maria Sanchez-Mico, Raquel Sanchez-Varo, Cristina Nuñez-Diaz, Laura Trujillo-Estrada, Jose Carlos Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica,

The role of microglial cells in the development and progression of Alzheimer's disease (AD) has not been elucidated. Here, we demonstrated the existence of a weak microglial response in human AD hippocampus which is in contrast to the massive microglial activation observed in APP-based models. Most importantly, microglial cells displayed ... Read more >>

Acta Neuropathol (Acta neuropathologica)
[2016, 132(6):897-916]

Cited: 47 times

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Asp32 and Asp228 determine the selective inhibition of BACE1 as shown by docking and molecular dynamics simulations.

Maricarmen Hernández-Rodríguez, José Correa-Basurto, Antonia Gutiérrez, Javier Vitorica, Martha C Rosales-Hernández,

Inhibition of β-site amyloid-β-protein precursor cleaving enzyme 1 (BACE1) represents a promising approach for the treatment of Alzheimer's disease (AD). However, the development of a selective BACE1 inhibitor is difficult due to its highly flexible catalytic site and homology to other aspartic proteases, including BACE2 and Cathepsin D (CTSD). Aiming ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2016, 124:1142-1154]

Cited: 9 times

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Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-β-Induced Neuronal Death.

Ana M Fernandez, Ruben Hervas, Manuel Dominguez-Fraile, Victoria Navarro Garrido, Patricia Gomez-Gutierrez, Miguel Vega, Javier Vitorica, Juan J Perez, Ignacio Torres Aleman,

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer's disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD-associated pathological inflammation, suggesting a potential new druggable target ... Read more >>

J Alzheimers Dis (Journal of Alzheimer's disease : JAD)
[2016, 52(4):1471-1478]

Cited: 13 times

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Metabolomic investigation of systemic manifestations associated with Alzheimer's disease in the APP/PS1 transgenic mouse model.

Raúl González-Domínguez, Tamara García-Barrera, Javier Vitorica, José Luis Gómez-Ariza,

There is growing evidence that Alzheimer's disease may be a widespread systemic disorder, so peripheral organs could be affected by pathological mechanisms occurring in this neurodegenerative disease. For this reason, a double metabolomic platform based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry was used ... Read more >>

Mol Biosyst (Molecular bioSystems)
[2015, 11(9):2429-2440]

Cited: 13 times

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Neuroinflammation in Alzheimer's disease.

Michael T Heneka, Monica J Carson, Joseph El Khoury, Gary E Landreth, Frederic Brosseron, Douglas L Feinstein, Andreas H Jacobs, Tony Wyss-Coray, Javier Vitorica, Richard M Ransohoff, Karl Herrup, Sally A Frautschy, Bente Finsen, Guy C Brown, Alexei Verkhratsky, Koji Yamanaka, Jari Koistinaho, Eicke Latz, Annett Halle, Gabor C Petzold, Terrence Town, Dave Morgan, Mari L Shinohara, V Hugh Perry, Clive Holmes, Nicolas G Bazan, David J Brooks, Stéphane Hunot, Bertrand Joseph, Nikolaus Deigendesch, Olga Garaschuk, Erik Boddeke, Charles A Dinarello, John C Breitner, Greg M Cole, Douglas T Golenbock, Markus P Kummer,

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which ... Read more >>

Lancet Neurol (The Lancet. Neurology)
[2015, 14(4):388-405]

Cited: 1441 times

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Metabolomics reveals significant impairments in the immune system of the APP/PS1 transgenic mice of Alzheimer's disease.

Raúl González-Domínguez, Tamara García-Barrera, Javier Vitorica, José Luis Gómez-Ariza,

Inflammatory processes and other failures related to the immune system are common features associated with Alzheimer's disease (AD), in both brain and the peripheral system. Thus, the study of the main organs of the immune system may have a great potential for the elucidation of pathological mechanisms underlying these abnormalities. ... Read more >>

Electrophoresis (Electrophoresis)
[2015, 36(4):577-587]

Cited: 12 times

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Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease.

Raúl González-Domínguez, Tamara García-Barrera, Javier Vitorica, José Luis Gómez-Ariza,

Metabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clinical practice it is necessary to corroborate these ... Read more >>

J Pharm Biomed Anal (Journal of pharmaceutical and biomedical analysis)
[2015, 107:378-385]

Cited: 19 times

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Increased levels of tumour necrosis factor alpha (TNFα) but not transforming growth factor-beta 1 (TGFβ1) are associated with the severity of congenital hydrocephalus in the hyh mouse.

Antonio-Jesús Jiménez, Luis-Manuel Rodríguez-Pérez, María-Dolores Domínguez-Pinos, María-Carmen Gómez-Roldán, María García-Bonilla, Ailec Ho-Plagaro, Ruth Roales-Buján, Sebastián Jiménez, María-Carmen Roquero-Mañueco, María-Isabel Martínez-León, María-Luisa García-Martín, Manuel Cifuentes, Bienvenido Ros, Miguel-Ángel Arráez, Javier Vitorica, Antonia Gutiérrez, José-Manuel Pérez-Fígares,

Here, we tested the hypothesis that glial responses via the production of cytokines such as transforming growth factor-beta 1 (TGFβ1) and tumour necrosis factor alpha (TNFα), which play important roles in neurodegenerative diseases, are correlated with the severity of congenital hydrocephalus in the hyh mouse model. We also searched for ... Read more >>

Neuropathol Appl Neurobiol (Neuropathology and applied neurobiology)
[2014, 40(7):911-932]

Cited: 7 times

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High throughput multiorgan metabolomics in the APP/PS1 mouse model of Alzheimer's disease.

Raúl González-Domínguez, Tamara García-Barrera, Javier Vitorica, José Luis Gómez-Ariza,

Metabolomics has demonstrated a great potential for the study of pathological mechanisms occurring in brain from Alzheimer's disease patients and transgenic models. However, its application to peripheral samples is not so common, although it can provide interesting information about systemic abnormalities underlying to disease. This work represents the first metabolomic ... Read more >>

Electrophoresis (Electrophoresis)
[2015, 36(18):2237-2249]

Cited: 6 times

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