En torno a la edición de los pliegos poéticos religiosos del siglo XVI

los pliegos religiosos en verso impresos durante el siglo XVI en España han sido puestas de manifiesto en reiteradas ocasiones. El estudio de su corpus, sin embargo, revela una de las líneas de investigación más interesantes para poder conocer de primera mano la tradición cultural y literaria transmitida por estos impresos durante el Quinientos. Este trabajo dará cuenta de los principales problemas que conlleva la edición de la literatura religiosa popular impresa en pliegos sueltos a lo largo del siglo XVI

Aquaporin 5 in Alzheimer's disease: a link between oral and brain pathology?

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Implication of salivary lactoferrin and periodontal-mediated infections in Alzheimer's disease

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Oxidative Stress in Tauopathies: From Cause to Therapy

Oxidative stress (OS) is the result of an imbalance between the production of reactive oxygen species (ROS) and the antioxidant capacity of cells. Due to its high oxygen demand, the human brain is highly susceptible to OS and, thus, it is not a surprise that OS has emerged as an essential component of the pathophysiology of several neurodegenerative diseases, including tauopathies. Tauopathies are a heterogeneous group of age-related neurodegenerative disorders characterized by the deposition of abnormal tau protein in the affected neurons. With the worldwide population aging, the prevalence of tauopathies is increasing, but effective therapies have not yet been developed. Since OS seems to play a key role in tauopathies, it has been proposed that the use of antioxidants might be beneficial for tau-related neurodegenerative diseases. Although antioxidant therapies looked promising in preclinical studies performed in cellular and animal models, the antioxidant clinical trials performed in tauopathy patients have been disappointing. To develop effective antioxidant therapies, the molecular mechanisms underlying OS in tauopathies should be completely understood. Here, we review the link between OS and tauopathies, emphasizing the causes of OS in these diseases and the role of OS in tau pathogenesis. We also summarize the antioxidant therapies proposed as a potential treatment for tauopathies and discuss why they have not been completely translated to clinical trials. This review aims to provide an integrated perspective of the role of OS and antioxidant therapies in tauopathies. In doing so, we hope to enable a more comprehensive understanding of OS in tauopathies that will positively impact future studies.This study has been funded by the “Instituto de Salud Carlos III” (ISCIII) through the projects CP21_00049, CP20_00007 and PI21_00183 and co-funded by the European Union.S

Standardizing Salivary Lactoferrin Measurements to Obtain a Robust Diagnostic Biomarker for Alzheimer's Disease

The search for new, robust, and reproducible biomarkers for Alzheimer's disease (AD) diagnosis is a challenge. We recently reported that salivary lactoferrin (Lf) could be presented as new biomarker candidate for AD, being both non-invasive and cost-effective, as well as having appropriate diagnostic performance for the clinical detection of AD subjects. Saliva is an attractive sample type for biomarker-based testing approaches for several other diseases; however, its composition may change under certain circumstances. It is therefore critical to maintain a consistent salivary handling protocol, considering possible extrinsic factors that may influence salivary Lf concentration. In this work, we analyzed salivary Lf concentration under different handling conditions and donor-dependent factors including age, inter-diurnal variations, physical activity, and pharmacological treatments. Our aim was to evaluate the influence of such conditions on salivary Lf concentration. In conclusion, we found that most of these extrinsic factors should be considered in the future when using Lf as a predictive biomarker for AD.This study was supported by Dr. Carro's grants from Instituto de Salud Carlos III (FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01)

Peregrinaciones y primeras peregrinas en Tierra Santa

El objetivo de este trabajo es el estudio del fenómeno de las peregrinaciones en Tierra Santa y en concreto los viajes de las primeras peregrinas. Para ello se analiza el marco histórico en el que se desarrollan estos viajes y las vidas de las primeras mujeres peregrinas con especial atención en el Itinerarium de Egeria y la Vita Melaniae.Departamento de Filología ClásicaGrado en Estudios Clásico

Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β (Aβ) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβ accumulation at the choroid plexus epithelium remain unclear. Aβ clearance, from the brain to the blood, involves Aβ carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD

Epigenetic silencing of OR and TAS2R genes expression in human orbitofrontal cortex at early stages of sporadic Alzheimer’s disease

Modulation of brain olfactory (OR) and taste receptor (TASR) expression was recently reported in neurological diseases. However, there is still limited evidence of these genes' expression in the human brain and the transcriptional regulation mechanisms involved remain elusive. We explored the possible expression and regulation of selected OR and TASR in the human orbitofrontal cortex (OFC) of sporadic Alzheimer's disease (AD) and non-demented control specimens using quantitative real-time RT-PCR and ELISA. Global H3K9me3 amounts were measured on OFC total histone extracts, and H3K9me3 binding at each chemoreceptor locus was examined through native chromatin immunoprecipitation. To investigate the potential interactome of the repressive histone mark H3K9me3 in OFC specimens, native nuclear complex co-immunoprecipitation (Co-IP) was combined with reverse phase-liquid chromatography coupled to mass spectrometry analysis. Interaction between H3K9me3 and MeCP2 was validated by reciprocal Co-IP, and global MeCP2 levels were quantitated. We found that OR and TAS2R genes are expressed and markedly downregulated in OFC at early stages of sporadic AD, preceding the progressive reduction in their protein levels and the appearance of AD-associated neuropathology. The expression pattern did not follow disease progression suggesting transcriptional regulation through epigenetic mechanisms. We discovered an increase of OFC global H3K9me3 levels and a substantial enrichment of this repressive signature at ORs and TAS2Rs proximal promoter at early stages of AD, ultimately lost at advanced stages. We revealed the interaction between H3K9me3 and MeCP2 at early stages and found that MeCP2 protein is increased in sporadic AD. Findings suggest MeCP2 might be implicated in OR and TAS2R transcriptional regulation through interaction with H3K9me3, and as an early event, it may uncover a novel etiopathogenetic mechanism of sporadic AD

Epigenetic silencing of OR and TAS2R genes expression in human orbitofrontal cortex at early stages of sporadic Alzheimer’s disease

Modulation of brain olfactory (OR) and taste receptor (TASR) expression was recently reported in neurological diseases. However, there is still limited evidence of these genes’ expression in the human brain and the transcriptional regulation mechanisms involved remain elusive. We explored the possible expression and regulation of selected OR and TASR in the human orbitofrontal cortex (OFC) of sporadic Alzheimer’s disease (AD) and non-demented control specimens using quantitative real-time RT-PCR and ELISA. Global H3K9me3 amounts were measured on OFC total histone extracts, and H3K9me3 binding at each chemoreceptor locus was examined through native chromatin immunoprecipitation. To investigate the potential interactome of the repressive histone mark H3K9me3 in OFC specimens, native nuclear complex co-immunoprecipitation (Co-IP) was combined with reverse phase-liquid chromatography coupled to mass spectrometry analysis. Interaction between H3K9me3 and MeCP2 was validated by reciprocal Co-IP, and global MeCP2 levels were quantitated. We found that OR and TAS2R genes are expressed and markedly downregulated in OFC at early stages of sporadic AD, preceding the progressive reduction in their protein levels and the appearance of AD-associated neuropathology. The expression pattern did not follow disease progression suggesting transcriptional regulation through epigenetic mechanisms. We discovered an increase of OFC global H3K9me3 levels and a substantial enrichment of this repressive signature at ORs and TAS2Rs proximal promoter at early stages of AD, ultimately lost at advanced stages. We revealed the interaction between H3K9me3 and MeCP2 at early stages and found that MeCP2 protein is increased in sporadic AD. Findings suggest MeCP2 might be implicated in OR and TAS2R transcriptional regulation through interaction with H3K9me3, and as an early event, it may uncover a novel etiopathogenetic mechanism of sporadic AD. Graphical abstrac

Potential role of aminoprocalcitonin in the pathogenesis of alzheimer disease

Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-b (Ab), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Ab-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Ab-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Ab-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target