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Author Antonia Gutierrez

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Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

David Baglietto-Vargas, Stefania Forner, Lena Cai, Alessandra C Martini, Laura Trujillo-Estrada, Vivek Swarup, Marie Minh Thu Nguyen, Kelly Do Huynh, Dominic I Javonillo, Kristine Minh Tran, Jimmy Phan, Shan Jiang, Enikö A Kramár, Cristina Nuñez-Diaz, Gabriela Balderrama-Gutierrez, Franklin Garcia, Jessica Childs, Carlos J Rodriguez-Ortiz, Juan Antonio Garcia-Leon, Masashi Kitazawa, Mohammad Shahnawaz, Dina P Matheos, Xinyi Ma, Celia Da Cunha, Ken C Walls, Rahasson R Ager, Claudio Soto, Antonia Gutierrez, Ines Moreno-Gonzalez, Ali Mortazavi, Andrea J Tenner, Grant R MacGregor, Marcelo Wood, Kim N Green, Frank M LaFerla,

The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. ... Read more >>

Nat Commun (Nature communications)
[2021, 12(1):2421]

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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]

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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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Author Correction: Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.

Amada R López de la Oliva, José A Campos-Sandoval, María C Gómez-García, Carolina Cardona, Mercedes Martín-Rufián, Fernando J Sialana, Laura Castilla, Narkhyun Bae, Carolina Lobo, Ana Peñalver, Marina García-Frutos, David Carro, Victoria Enrique, José C Paz, Raghavendra G Mirmira, Antonia Gutiérrez, Francisco J Alonso, Juan A Segura, José M Matés, Gert Lubec, Javier Márquez,

Sci Rep (Scientific reports)
[2021, 11(1):249]

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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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Generation of oligodendrocytes and establishment of an all-human myelinating platform from human pluripotent stem cells.

Juan Antonio García-León, Beatriz García-Díaz, Kristel Eggermont, Laura Cáceres-Palomo, Katrien Neyrinck, Rodrigo Madeiro da Costa, José Carlos Dávila, Anne Baron-Van Evercooren, Antonia Gutiérrez, Catherine M Verfaillie,

Oligodendrocytes (OLs) are responsible for myelin production and metabolic support of neurons. Defects in OLs are crucial in several neurodegenerative diseases including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). This protocol describes a method to generate oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells (hPSCs) in only ~20 ... Read more >>

Nat Protoc (Nature protocols)
[2020, 15(11):3716-3744]

Cited: 2 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]

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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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The Insulin Receptor in Astrocytes is Involved in the Entrance of Circulating Insulin into the Brain

Ana Fernandez, Navarrete, Jose Carlos Davila, Cristina Garcia-Caceres, Rocio Palenzuela, Samuel Ruiz de Martin Esteban, Ricardo Mostany, Matthias Tschöp, Antonia Gutierrez, Ignacio Torres Aleman,

Circulating insulin enters into the brain through mechanisms that are not yet entirely understood. We now report that mice lacking insulin receptors (IR) in astrocytes show reduced uptake of circulating insulin and blunted brain responses to this circulating hormone, suggesting that astrocytes form part of the cellular pathway in the ... Read more >>

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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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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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Astrocytes: From the Physiology to the Disease.

Laura Trujillo-Estrada, Angela Gomez-Arboledas, Stefânia Forner, Alessandra Cadete Martini, Antonia Gutierrez, David Baglietto-Vargas, Frank M LaFerla,

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 ... Read more >>

Curr Alzheimer Res (Current Alzheimer research)
[2019, 16(8):675-698]

Cited: 3 times

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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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A Distinct Metabolite Profile Correlates with Neurodegenerative Conditions and the Severity of Congenital Hydrocephalus.

María García-Bonilla, María L García-Martín, M Carmen Muñoz-Hernández, Dolores Domínguez-Pinos, María I Martínez-León, Ana Peñalver, Laura Castilla, Francisco J Alonso, Javier Márquez, Kirill Shumilov, Ramón Hidalgo-Sánchez, Antonia Gutiérrez, Patricia Páez-González, Antonio J Jiménez,

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated with increased intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage, and astrocytic reaction. The aim of this study was to identify whether a metabolite profile revealing tissue responses according to the severity of hydrocephalus can be detected. The hyh mutant mouse used ... Read more >>

J Neuropathol Exp Neurol (Journal of neuropathology and experimental neurology)
[2018, 77(12):1122-1136]

Cited: 2 times

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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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Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer's disease.

David Baglietto-Vargas, Gilberto Aleph Prieto, Agenor Limon, Stefania Forner, Carlos J Rodriguez-Ortiz, Kenji Ikemura, Rahasson R Ager, Rodrigo Medeiros, Laura Trujillo-Estrada, Alessandra C Martini, Masashi Kitazawa, Jose C Davila, Carl W Cotman, Antonia Gutierrez, Frank M LaFerla,

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impairs memory and causes cognitive and psychiatric deficits. New evidences indicate that AD is conceptualized as a disease of synaptic failure, although the molecular and cellular mechanisms underlying these defects remain to be elucidated. Determining the timing and nature of the ... Read more >>

Aging Cell (Aging cell)
[2018, 17(4):e12791]

Cited: 20 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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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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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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N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson's disease.

Patricia García-Sanz, Lorena Orgaz, Guillermo Bueno-Gil, Isabel Espadas, Eva Rodríguez-Traver, Jaime Kulisevsky, Antonia Gutierrez, José C Dávila, Rosa A González-Polo, José M Fuentes, Pablo Mir, Carlos Vicario, Rosario Moratalla,

<h4>Background</h4>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 ... Read more >>

Mov Disord (Movement disorders : official journal of the Movement Disorder Society)
[2017, 32(10):1409-1422]

Cited: 33 times

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

Ana Peñalver, José A Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, Mercedes Martín-Rufián, Guillermo Estivill-Torrús, Raquel Sánchez-Varo, Francisco J Alonso, Mercedes Pérez-Hernández, María I Colado, Antonia Gutiérrez, Fernando Rodríguez de Fonseca, Javier Márquez,

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 LPA<sub>1</sub> receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA<sub>1</sub> mice. ... Read more >>

Front Mol Neurosci (Frontiers in molecular neuroscience)
[2017, 10:278]

Cited: 6 times

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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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