A5011432006- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Nerve injury and regeneration
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Biotin and Related Studies
- RNA regulation and disease
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- Memory and Neural Mechanisms
- Hippo pathway signaling and YAP/TAZ
- Chemokine receptors and signaling
- Cancer-related molecular mechanisms research
- Calpain Protease Function and Regulation
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Autoimmune and Inflammatory Disorders Research
- S100 Proteins and Annexins
- MicroRNA in disease regulation
- Glutathione Transferases and Polymorphisms
- ATP Synthase and ATPases Research
- Cell Adhesion Molecules Research
King's College London
2021-2023
Johannes Gutenberg University Mainz
2018-2023
University Medical Center of the Johannes Gutenberg University Mainz
2018-2023
Centro de Biología Molecular Severo Ochoa
2012-2019
Universidad Autónoma de Madrid
2012-2019
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2019
Centro de Investigación Biomédica en Red
2015-2018
Instituto de Salud Carlos III
2012-2018
Consejo Superior de Investigaciones Científicas
2012-2018
The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of tauopathies. Excess can be released into extracellular medium physiological or pathological manner to internalized by surrounding neurons-a process that contributes spread this throughout brain. Such spreading may correlate with progression abovementioned diseases. In addition neurons, other cells. Here we demonstrate microglia take up vitro and vivo. regard, from primary cultures soluble (human...
Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis an important neuron/microglia communication mechanism.We studied clearance by microglia both in vitro (microglia primary cultures treated with Cy5-Tau, affinity chromatography study binding CX3CR1, Tau-CX3CL1 competition assays) vivo (stereotaxic injection Cy5-Tau into WT CX3CR1-/- mice). expression CX3CL1 microglial phagocytic phenotype were brain tissue samples from AD...
Microglia are immune cells that play a crucial role in maintaining brain homeostasis. Among the mechanisms of communication between microglia and neurons, CX3CL1/CX3CR1 axis exerts central modulatory role. Animals lacking CX3CR1 microglial receptor (CX3CR1−/− mice) exhibit marked alterations not only but also neurons located various regions brain. Here we show depletion leads to deficient synaptic integration adult-born granule dentate gyrus (DG), both at afferent efferent level. Regarding...
Abstract Astrocytes have essential functions in brain homeostasis that are established late differentiation, but the mechanisms underlying functional maturation of astrocytes not well understood. Here we identify extensive transcriptional changes occur during murine astrocyte vivo accompanied by chromatin remodelling at enhancer elements. Investigating a cell culture model revealed vitro-differentiated lack expression many mature astrocyte-specific genes, including genes for transcription...
Article19 May 2016Open Access Transparent process Novel function of Tau in regulating the effects external stimuli on adult hippocampal neurogenesis Noemí Pallas-Bazarra Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Search for more papers by this author Jerónimo Jurado-Arjona Marta Navarrete Jose A Esteban Félix Hernández Sciences Faculty, Autonoma University, Jesús Ávila...
Tau protein is a microtubule-associated found in the axonal compartment that stabilizes neuronal microtubules under normal physiological conditions. metabolism has attracted much attention because of its role neurodegenerative disorders called tauopathies, mainly Alzheimer disease. Here, we review recent findings suggesting outgrowth subgranular zone during adult hippocampal neurogenesis requires dynamic microtubule network and tau facilitates to maintain cytoskeleton. Those functions are...
Both familial and sporadic forms of Alzheimer disease (AD) present memory impairments. It has been proposed that these impairments are related to inflammation in relevant brain areas such as the hippocampus. Whether peripherally triggered neuron-driven produce similar equally reversible alterations is a matter discussion. Here we studied effects ibuprofen administration on AD mouse model overexpressing GSK-3β presents severe inflammation. We compared with those observed based chronic...
Gene therapy for Niemann-Pick type A disease is safe in nonhuman primates and has therapeutic effects a mouse model.
Most adult hippocampal neural stem cells (NSCs) remain quiescent, with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger the transition from quiescence to activation are still poorly understood. Here, we found activity of transcriptional co-activator Yap1 be enriched in NSCs. Genetic deletion led significant reduction relative proportion NSCs, supporting physiological role regulating activation. Overexpression wild-type NSCs did not...
Abstract Tau is a neuronal microtubule-associated protein with countless physiological functions. Although the detrimental effects of insoluble aggregated have been widely studied, recent evidence supports notion that soluble (composed mostly monomers and dimers) also toxic for neurons. Here we evaluated long-term impact single stereotaxic injection human on hippocampal granule neurons in mice. At ultrastructural level, reduced number afferent synapses caused dramatic depletion synaptic...
In rodents, the hippocampal dentate gyrus gives rise to newly generated granule cells (DGCs) throughout life. This process, named adult neurogenesis (AHN), converges in functional integration of mature DGCs into trisynaptic circuit. Environmental enrichment (EE) is one most potent positive regulators AHN. paradigm includes combination three major stimulatory components, namely increased physical activity, constant cognitive stimulation, and higher social interaction. this regard,...
In the adult hippocampal dentate gyrus, newborn granule cells grow dendrites into molecular layer and send axons CA3 region. Several markers have been used to analyze production of these new neurons; however, no good for described. Here we demonstrate that tau protein isoform with three microtubule binding domains (3R-Tau) is a marker those following an antigen retrieval protocol. By using retrovirus-mediated GFP transduction, can be detected in period 7-14 days after viral infection. We...
Failures in neurotrophic support and signalling play key roles Alzheimer's disease (AD) pathogenesis. We previously demonstrated that downregulation of the neurotrophin effector Kinase D interacting substrate (Kidins220) by excitotoxicity cerebral ischaemia contributed to neuronal death. This downregulation, triggered through overactivation N-methyl-d-aspartate receptors (NMDARs), involved proteolysis Kidins220 calpain transcriptional inhibition. As is at basis AD aetiology, we hypothesized...
Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since activates protein kinase D1 (PKD1) tumor cells, we investigated the effect of excitotoxicity on PKD1 activity. Unexpectedly, find that provokes an early inactivation dephosphorylation-dependent mechanism mediated by phosphatase-1 (PP1) dual specificity (DUSP1). This step turns off IKK/NF-κB/SOD2 antioxidant pathway. Neuronal pharmacological inhibition...
Prolonged seizures (status epilepticus) may drive hippocampal dysfunction and epileptogenesis, at least partly, through an elevation in neurogenesis, dysregulation of migration aberrant dendritic arborization newly-formed neurons. MicroRNA-22 was recently found to protect against the development epileptic foci, but mechanisms remain incompletely understood. Here, we investigated contribution microRNA-22 status epilepticus-induced adult neurogenesis. Status epilepticus induced by...
Glycogen synthase kinase-3β (GSK-3β) is a serine-threonine kinase implicated in multiple processes and signaling pathways. Its dysregulation associated with different pathological conditions including Alzheimer's disease (AD). Here we demonstrate how changes GSK-3β activity and/or levels regulate the production subsequent secretion of fractalkine, chemokine involved immune response that has been linked to AD other neurological disorders. Treatment primary cultured neurons inhibitors such as...