Avila, J. (Jesús)

Filtering

2005 - 20093

Settings

Author search.filters.isAuthorOfPublication.2757ce4f-661c-40c0-987f-bc824240a9b6

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Immunotherapy for neurological diseases
    (Elsevier, 2008) Rivest, S. (Serge); Schwartz, M. (Michal); Avila, J. (Jesús); Khoury, S.J. (Samia J.); Obeso, J.A. (José A.); Moreno, B. (Beatriz); Martino, G. (Gianvito); Acarin, L. (Laia); Ferrer, I. (Isidro); Villoslada, P. (Pablo); McGeer, P. (Patrick); Appel, S. (Stanley); Montalban, X. (Xavier); Melero, I. (Ignacio); Uccelli, A. (Antonio); Delgado, M. (Mario); Pablos, J.L. (José L.)
    The burden of neurological diseases in western societies has accentuated the need to develop effective therapies to stop the progression of chronic neurological diseases. Recent discoveries regarding the role of the immune system in brain damage coupled with the development of new technologies to manipulate the immune response make immunotherapies an attractive possibility to treat neurological diseases. The wide repertoire of immune responses and the possibility to engineer such responses, as well as their capacity to promote tissue repair, indicates that immunotherapy might offer benefits in the treatment of neurological diseases, similar to the benefits that are being associated with the treatment of cancer and autoimmune diseases. However, before applying such strategies to patients it is necessary to better understand the pathologies to be targeted, as well as how individual subjects may respond to immunotherapies, either in isolation or in combination. Due to the powerful effects of the immune system, one priority is to avoid tissue damage due to the activity of the immune system, particularly considering that the nervous system does not tolerate even the smallest amount of tissue damage.
  • Thumbnail Image
    Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease
    (IOS Press, 2009-01-22) Frechilla, D. (Diana); Avila, J. (Jesús); Perez-Mediavilla, L.A. (Luis Alberto); Ricobaraza, A. (Ana); Simon, A.M. (Ana María); Cuadrado-Tejedor, M. (Mar); Schiapparelli, L. (Lucio); Rio, J. (Joaquín) del; Raquel; Escribano, L. (Luis)
    Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in the hippocampus leading to cognitive impairment in a model of AD.
  • Thumbnail Image
    Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice
    (Elsevier, 2005) Ortiz, L. (Lourdes); Gomez-Isla, T. (Teresa); Avila, J. (Jesús); Perez-Mediavilla, L.A. (Luis Alberto); Ramos, P. (Pilar); Catena, S. (Silvia); Cabodevilla, F. (Felipe); Perez, M. (Mar); Samaranch, L. (Lluis); Ribe, E. (Elena M.); Ferrer, I. (Isidro); Nieto, M. (María); Puig, B. (Berta); Moran, M.A. (María Asunción); Cuadrado-Tejedor, M. (Mar); Sesma, T. (Teresa); Gich, I. (Ignasi); Sanchez, B. (Belén); Lim, F. (Filip)
    Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.