A5033320342- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurological Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Neurotransmitter Receptor Influence on Behavior
- Mast cells and histamine
- Immune cells in cancer
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Ion Transport and Channel Regulation
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Nerve injury and regeneration
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Biochemical Acid Research Studies
- 14-3-3 protein interactions
- Pesticide Exposure and Toxicity
- Chemical Synthesis and Analysis
- Retinal Development and Disorders
- Polyamine Metabolism and Applications
Universidad de Sevilla
2014-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2024
Instituto de Biomedicina de Sevilla
2012-2024
Hospital Universitario Virgen del Rocío
2011-2024
Centro de Investigación Biomédica en Red
2014-2024
Instituto de Salud Carlos III
2024
Consejo Superior de Investigaciones Científicas
2011-2012
Université Paris Cité
1997
Inserm
1994-1995
Centre Paul Broca
1994-1995
Although the microglial activation is concomitant to Alzheimer's disease, its precise role (neuroprotection vs neurodegeneration) has not yet been resolved. Here, we show existence of an age-dependent phenotypic change in hippocampus PS1xAPP model, from alternative state with Aβ phagocytic capabilities (at 6 months) a classic cytotoxic phenotype (expressing TNF-α and related factors) at 18 months age. This switch was coincident high levels soluble oligomers significant pyramidal...
Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, immune system and microglial cells (as part cerebral immunity) play central role. other degenerative processes, Alzheimer's disease (AD), role microglia is far to be elucidated. this "mini-review" article, we briefly highlight our recent data comparing response between...
Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components intermediate filaments, is common feature in brains Alzheimer's patients. astrocytes are found close association with neuritic plaques; however, the precise role these glial cells disease pathogenesis unknown. In this study, using immunohistochemical techniques light electron microscopy, we report that plaque-associated reactive enwrap, engulf may digest presynaptic dystrophies...
Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer's disease (AD). In this work we have characterized the plaque-associated neuritic pathology hippocampus of young (4- to 6-month-old) PS1M146L/APP751SL mice model, as initial degenerative process underlying functional disturbance prior loss. Neuritic accounted for almost all fibrillar deposits an axonal origin dystrophies was demonstrated. The induction autophagy evidenced by increased...
Neurotrophins, activating the PI3K/Akt signaling pathway, control neuronal survival and plasticity. Alterations in NGF, BDNF, IGF-1, or insulin are implicated pathogenesis of Alzheimer disease. We have previously characterized a bigenic PS1×APP transgenic mouse displaying early hippocampal Aβ deposition (3 to 4 months) but late (17 18 neurodegeneration pyramidal cells, paralleled accumulation soluble oligomers. hypothesized that PI3K/Akt/GSK-3β pathway could be involved this apparent...
The role of microglial cells in the development and progression Alzheimer's disease (AD) has not been elucidated. Here, we demonstrated existence a weak response human AD hippocampus which is contrast to massive activation observed APP-based models. Most importantly, displayed prominent degenerative profile (dentate gyrus > CA3 CA1 parahippocampal gyrus), including fragmented dystrophic processes with spheroids, reduced numerical density, significant decrease area surveillance ("microglial...
Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of CNS pathogenesis Alzheimer's disease (AD). However, contribution nonparenchymal or brain-infiltrated to progression remains be demonstrated. Here, we show that monocyte-derived (MDC) invade brain parenchyma advanced stages AD continuum using transcriptional analysis immunohistochemical characterization post-mortem human hippocampus. Our findings demonstrated high proportion (60%) demented Braak...
Iodoproxyfan, i.e., 3-(1H-imidazol-4-yl)propyl-(4-iodophenyl)-methyl ether, is a novel potent and selective histamine H3 receptor antagonist. [125I]Iodoproxyfan binding to membranes of the rat striatum was reversible saturable. Specific defined with 1 microM (R)-alpha-methylhistamine corresponded 65% total at 30 pM. Scatchard analysis indicated Kd 65 pM maximal capacity 78 fmol/mg protein. The specificity receptors demonstrated by its pharmacological profile. A series agonists inhibited...
Abstract Background Axonal pathology might constitute one of the earliest manifestations Alzheimer disease. dystrophies were observed in Alzheimer’s patients and transgenic models at early ages. These axonal could reflect disruption transport accumulation multiple vesicles local points. It has been also proposed that interfere with normal intracellular proteolysis. In this work, we have investigated progression hippocampal possible implication Abeta production young (6 months) aged (18...
Specific neuronal networks are preferentially affected in the early stages of Alzheimer's disease (AD). The distinct subpopulations hippocampal inhibitory GABAergic system have been shown to display differential vulnerability neurodegeneration
Abstract Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid‐β plaques in Alzheimer's disease (AD). We have previously shown that reactive enwrap, phagocytose, degrade synapses the hippocampus of APP mice AD patients, but affecting less than 7% suggesting reduced phagocytic capacity AD. Here, we aimed to gain insight into underlying mechanisms by analyzing primary astrocyte cultures phagocytose isolated (synaptoneurosomes, SNs) from...
The progressive cognitive decline leading to dementia in Alzheimer's disease (AD) patients is the consequence of a severe loss synapses and neurons affecting particular cell subpopulations selected brain areas, with subiculum being one t
Abstract In Alzheimer’s disease (AD), and other tauopathies, microtubule destabilization compromises axonal synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, effect stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated impact brain-penetrant microtubule-stabilizing...
Abstract Increased neuroinflammatory reaction is frequently observed during normal brain aging. However, a direct link between neuroinflammation and neurodegeneration aging has not yet been clearly shown. Here, we have characterized the age‐related hippocampal inflammatory processes potential relation with neurodegeneration. The mRNA expression of pro‐inflammatory cytokines IL‐1β tumor necrosis factor‐α (TNF‐α), iNOs enzyme was significantly increased in aged hippocampus. Accordingly,...
We have evaluated the effects of a direct infusion histamine, as mediator inflammatory response, in substantia nigra, striatum, medial septum, and lemniscus. Injection 100 250 nmol histamine nigra produced selective damage dopaminergic neurons evidenced by loss tyrosine hydroxylase mRNA-expressing cells, hydroxylase-immunolabeled-positive cell bodies, dopamine 3,4-dihydroxyphenylacetic acid levels. In parallel we found an acute response manifested glial fibrillary acidic...
Abstract: In the present communication we have investigated allosteric coupling between γ‐aminobutyric acid A (GABA ) receptor and pharmacologically different benzodiazepine (BZD) subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I type II) been classically defined using CL 218.872. However, zolpidem, three identified by binding displacement experiments membranes. These displayed high, low, very low affinity for zolpidem. The distribution high‐...
Alzheimer's disease (AD) is characterized by the abnormal accumulation of extracellular beta-amyloid (Abeta) plaques, intracellular hyperphosphorylated tau, progressive synaptic alterations, axonal dystrophies, neuronal loss and deterioration cognitive capabilities patients. However, no effective disease-modifying treatment has been yet developed. In this work we have evaluated whether chronic lithium could ameliorate neuropathology evolution our well PS1M146LxAPPSwe-London mice model.Though...
Alzheimer's disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over past two decades, multiple studies have focused on elucidating causative factors underlying memory defects patients. In this regard, new evidence linking disease-related pathology and neuronal stem cells suggests hippocampal neurogenesis impairment an important factor these deficits. However, because of conflicting results, impact Aβ neurogenesis/gliogenesis...