Page 89 - CIBERER2016-ENG

Most relevant scientific articles
• Alquezar C., de la Encarnacion A., Moreno F., Lopez de Munain A., Martin-Requero A.. Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral
cells from frontotemporal dementia-linked granulin mutation carriers. Journal of Psychiatry and Neuroscience. 2016;41(4):225-239.
• Alquezar C., Salado I.G., De La Encarnacion A., Perez D.I., Moreno F., Gil C. et al. Targeting TDP-43 phosphorylation by Casein Kinase-1δ inhibitors: A novel strategy for the treatment of frontotemporal dementia. Molecular Neurodegeneration. 2016;11(1).
• Horrillo A., Porras G., Ayuso M.S., Gonzalez-Manchon C. Loss of endothelial barrier integrity in mice with conditional ablation of podocalyxin (Podxl) in endothelial cells. European Journal of Cell Biology. 2016.
• Wojsiat J., Laskowska-Kaszub K., Alquezar C., Bialopiotrowicz E., Esteras N., Zdioruk M. et al. Familial Alzheimer’s Disease Lymphocytes Respond Differently Than Sporadic Cells to Oxidative Stress: Upregulated p53-p21 Signaling Linked with Presenilin 1 Mutants. Molecular Neurobiology. 2016;1-16.
• Nunez-Gomez E., Pericacho M., Ollauri-Ibanez C., Bernabeu C., Lopez-Novoa J.M. The role of endoglin in post-ischemic revascularization. Angiogenesis. 2016;1-24.
Hightlights
We have continued the study of the mechanisms involved in the vasculitis of mice lacking podocalyxin (Podxl) in the vascular endothelium. In addition to regulating endothelial permeability by interacting with intracellular proteins that modulate the actin cytoskeleton, our results suggest that Podxl is an essential component of the endothelial glycocalyx by regulating leukocyte adhesion and trafficking. This is of great interest because the injury of the glycocalyx underlies many vascular diseases and the role and relevance of its components is not known.
In collaboration with unit 707 of CIBERER, we discovered a new role for endoglin in the adhesion of platelets to the endothelium mediated by the integrin aIIbß3, whose alteration could contribute to the bleeding of patients with hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber syndrome. We continued to study the mechanisms that cause cell death in Alzheimer’s disease (AD), frontotemporal dementia (FTLD-TDP), and other neurodegenerative diseases. The work focuses on cell cycle sysfunction, apoptosis, mitochondrial impairment, oxidative damage, and protein degradation using in vivo model
of neurodegeneration and in vitro culture of cells, including peripheral cells from patients. We have used lymphoblastoid cell lines from patients as a platform to test the therapeutic potential of certain drugs impacting these processes for the treatment of AD and FTLD-TDP. In particular, we have studied the effects of new indazol derivatives, with activity as agonists of cannabinoid receptor of type 2, and novel selective inhibitors of Casein kinase-1 and CDC7 to decrease the phosphorylation of TDP-43.
Patent PCT / ES20167070906, 16-12-2016. Title of the invention: A new family of carboline derivatives of 1-indazolyl with properties of cannabinoids and/or cholinergic and/or regulatory peptide beta-amyloid. Inventors: JA Páez Prosper, NE Campillo Martín, C Pérez Martín, PJ González Naranjo, M Pérez Macías,
M López de Ceballos, A Martín Requero, C Alquézar Burillo, MI Martín Fontelles, MR García Moreno, EM Sánchez Robles, J Romero Paredes
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research groups 89