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Highlights
Institution: Agencia Estatal Consejo Superior de Investigaciones Científicas Contact: Centro de Investigaciones Biologicas · C/ Ramiro de Maéztu, 9 . 28040 Madrid . Tel .: (+34) 91 837 31 12 · E .mail:cgmanchon@cib .csic .es http://www .cib .csic .es/es/grupo .php?idgrupo=58” - https://www .cib .csic .es/es/grupo .php?idgrupo=57
• The generation and phenotypic characterization of “knockout” mice with conditional ablation of CD40L at different stages of hematopoietic development has provided relevant results to understand the pathogenesis and clinical manifestations of X-linked hyper-IgM syndrome due to mutations in the Cd40lg gene (ORPHA # 69712) .
• We have developed a mouse model lacking podocalicina (Podxl) in the vascular endothelium that represents an excellent tool for studying human vasculitis (ORPHA52759) and the mechanisms con- troling vascular permeability .
• We conducted an epidemiological study in collaboration with the research group of doctors Vincent and Rivera (Hospital Morales Meseguer, Murcia) on the incidence and identification of new mutants and diagnostic difficulties of inherited platelet diseases in the Iberian Peninsula . In this study, 14 hos- pitals have provided a total of 70 cases of 8 different disorders .
• We are interested in mechanisms that cause cell death in disorders such as Alzheimer’s disease (AD), frontotemporal dementia (FTLD) and other neurodegenerative disorders, in order to identify potential therapeutic targets and to find useful biomarkers for the early diagnosis and/or track disease status . The work focuses on cell cycle dysfuntion, apoptosis, mitochondrial impairment, oxidative damage, and protein degradation using in vivo models of neurodegeneration and in vitro culture of cells, inclu- ding peripheral cells from patients . Main findings can be summarized as follows:
1) We have detected altered gene expression in lymphocytes and brain of a murine model of familial AD, as well as in lymphocytes of AD patients .
2) The increased levels of calmodulin found in lymphocytes and plasma of AD patients may serve as a biomarker for early diagnosis of AD .
3) We have identified potential therapeutic targets in the Wn5a/CamKII/ERK1/2/CDK6/pRB signaling pathway for the treatment of progranulin-linked FTLD (ORPHA#98929) .
4) We began studies aimed at the repositioning of drugs for the treatment of idiopathic Parkinson disease .
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