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Author Juan Antonio Garcia Leon

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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]

Cited: 0 times

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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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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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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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Generation of a human induced pluripotent stem cell-based model for tauopathies combining three microtubule-associated protein TAU mutations which displays several phenotypes linked to neurodegeneration.

Juan Antonio García-León, Alfredo Cabrera-Socorro, Kristel Eggermont, Ann Swijsen, Joke Terryn, Raheem Fazal, FatemehArefeh Nami, Laura Ordovás, Ana Quiles, Frederic Lluis, Lutgarde Serneels, Keimpe Wierda, Annerieke Sierksma, Mohamed Kreir, Francisco Pestana, Philip Van Damme, Bart De Strooper, Lieven Thorrez, Andreas Ebneth, Catherine M Verfaillie,

<h4>Introduction</h4>Tauopathies are neurodegenerative diseases characterized by TAU protein-related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant TAU animal models are available, but none of them faithfully recapitulates human pathology and are not suitable for drug screening.<h4>Methods</h4>To create a new in vitro tauopathy model, we generated a footprint-free triple MAPT-mutant ... Read more >>

Alzheimers Dement (Alzheimer's & dementia : the journal of the Alzheimer's Association)
[2018, 14(10):1261-1280]

Cited: 9 times

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SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells.

Juan Antonio García-León, Manoj Kumar, Ruben Boon, David Chau, Jennifer One, Esther Wolfs, Kristel Eggermont, Pieter Berckmans, Nilhan Gunhanlar, Femke de Vrij, Bas Lendemeijer, Benjamin Pavie, Nikky Corthout, Steven A Kushner, José Carlos Dávila, Ivo Lambrichts, Wei-Shou Hu, Catherine M Verfaillie,

Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive ... Read more >>

Stem Cell Reports (Stem cell reports)
[2018, 10(2):655-672]

Cited: 15 times

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The CD4+ T-cell subset lacking expression of the CD28 costimulatory molecule is expanded and shows a higher activation state in multiple sclerosis.

María Jesús Pinto-Medel, Juan Antonio García-León, Begoña Oliver-Martos, Carlos López-Gómez, Gloria Luque, Carlos Arnáiz-Urrutia, Teresa Orpez, Carmen Marín-Bañasco, Oscar Fernández, Laura Leyva,

Multiple sclerosis (MS) is a chronic debilitating disease, in which T-cells are considered to play a pivotal role. CD28 is the quintessential costimulatory molecule on T-cells and its expression declines progressively with repeated stimulations, leading to the generation of CD28(-) T-cells. Our aim was to examine whether CD4(+)CD28(-) T-cells were ... Read more >>

J Neuroimmunol (Journal of neuroimmunology)
[2012, 243(1-2):1-11]

Cited: 11 times

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TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis.

Carlos López-Gómez, Oscar Fernández, Juan Antonio García-León, María Jesús Pinto-Medel, Begoña Oliver-Martos, Jesús Ortega-Pinazo, Margarita Suardíaz, Lucía García-Trujillo, Cristina Guijarro-Castro, Julián Benito-León, Isidro Prat, Jezabel Varadé, Roberto Álvarez-Lafuente, Elena Urcelay, Laura Leyva,

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor ... Read more >>

PLoS One (PloS one)
[2011, 6(7):e21766]

Cited: 11 times

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Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis.

Antonio Alcina, Maria Fedetz, Oscar Fernández, Albert Saiz, Guillermo Izquierdo, Miguel Lucas, Laura Leyva, Juan-Antonio García-León, María Del Mar Abad-Grau, Iraide Alloza, Alfredo Antigüedad, María J Garcia-Barcina, Koen Vandenbroeck, Jezabel Varadé, Belén de la Hera, Rafael Arroyo, Manuel Comabella, Xavier Montalban, Natalia Petit-Marty, Arcadi Navarro, David Otaegui, Javier Olascoaga, Yolanda Blanco, Elena Urcelay, Fuencisla Matesanz,

<h4>Background and aim</h4>Several studies have highlighted the association of the 12q13.3-12q14.1 region with coeliac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis (MS); however, the causal variants underlying diseases are still unclear. The authors sought to identify the functional variant of this region associated with MS.<h4>Methods</h4>Tag-single nucleotide polymorphism (SNP) ... Read more >>

J Med Genet (Journal of medical genetics)
[2013, 50(1):25-33]

Cited: 29 times

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Kinetics and incidence of anti-natalizumab antibodies in multiple sclerosis patients on treatment for 18 months.

Begoña Oliver, Oscar Fernández, Teresa Orpez, Marcos Papais Alvarenga, María Jesús Pinto-Medel, Miguel Guerrero, Antonio León, José Carlos López-Madrona, Rafael Maldonado-Sánchez, Juan Antonio García-León, Gloria Luque, Victoria Fernández, Laura Leyva,

Natalizumab is a monoclonal antibody shown to be highly effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Patients treated with natalizumab can develop antibodies directed against this agent that may affect the efficacy and safety of the drug. In this observational study, the kinetics of the appearance and the ... Read more >>

Mult Scler (Multiple sclerosis (Houndmills, Basingstoke, England))
[2011, 17(3):368-371]

Cited: 17 times

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