An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents beta-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans

The authors gratefully acknowledge the funding support of FEDER/Junta de AndaluciaConsejeria de Economia y Conocimiento, Grant B-AGR-193-UGR18. Also grant PID2019-106778RBI00, funded by MCIN/AEI/10.13039/501100011033 FEDER "Una manera de hacer Europa".Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like A beta- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred mu g/mL of extract treatment revealed prevention of oxidative stress and a delay in A beta-induced paralysis related with a lower presence of A beta aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects.FEDER/Junta de AndaluciaConsejeria de Economia y Conocimiento B-AGR-193-UGR18 PID2019-106778RBI00 MCIN/AEI/10.13039/50110001103

Amyloid β-but not Tau-induced neurotoxicity is suppressed by Manuka honey via HSP-16.2 and SKN-1/Nrf2 pathways in an in vivo model of Alzheimer’s disease

Alzheimer’s is a chronic degenerative disease of the central nervous system considered the leading cause of dementia in the world. It is characterized by two etiopathological events related to oxidative stress: the aggregation of β-amyloid peptide and the formation of neurofibrillary tangles of hyperphosphorylated Tau protein in the brain. The incidence of this disease increases with age and has been associated with inadequate lifestyles. Some natural compounds have been shown to improve the hallmarks of the disease. However, despite its potential, there is no scientific evidence about Manuka honey (MH) in this regard. In the present work we evaluated the effect of MH on the toxicity induced by Aβ aggregation and Tau in a Caenorhabditis elegans model. Our results demonstrated that MH was able to improve indicators of oxidative stress and delayed Aβ-induced paralysis in the AD model CL4176 through HSP-16.2 and SKN-1/ NRF2 pathways. Nevertheless, its sugar content impaired the indicators of locomotion (an indicator of tau neurotoxicity) in both the transgenic strain BR5706 and in the wild-type N2 worms.MCIN/AEI FPU2017/04358FSE "El FSE invierte en tu futuro" FPU2018/05301JdC-I post-doctoral contract - NextGenerationEU IJC2020-043910-IFEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento B-AGR-193-UGR1

An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents β-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans

Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like Aβ- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred μg/mL of extract treatment revealed prevention of oxidative stress and a delay in Aβ-induced paralysis related with a lower presence of Aβ aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects

Natural Bioactive Products and Alzheimer’s Disease Pathology: Lessons from Caenorhabditis elegans Transgenic Models

Alzheimer’s disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and A -induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention

An Olive-Derived Extract 20% Rich in Hydroxytyrosol Prevents β-Amyloid Aggregation and Oxidative Stress, Two Features of Alzheimer Disease, via SKN-1/NRF2 and HSP-16.2 in Caenorhabditis elegans.

Olive milling produces olive oil and different by-products, all of them very rich in different bioactive compounds like the phenolic alcohol hydroxytyrosol. The aim of the present study was to investigate the effects of an olive fruit extract 20% rich in hydroxytyrosol on the molecular mechanisms associated with Alzheimer disease features like Aβ- and tau- induced toxicity, as well as on oxidative stress in Caenorhabditis elegans. Moreover, characterization of the extracts, regarding the profile and content of phenolics, as well as total antioxidant ability, was investigated. The study of lethality, growth, pharyngeal pumping, and longevity in vivo demonstrated the lack of toxicity of the extract. One hundred μg/mL of extract treatment revealed prevention of oxidative stress and a delay in Aβ-induced paralysis related with a lower presence of Aβ aggregates. Indeed, the extract showed the ability to avoid a certain degree of proteotoxicity associated with aggregation of the tau protein. According to RNAi tests, SKN-1/NRF2 transcription factor and the overexpression of HSP-16.2 were mechanistically associated in the observed effects

El Proyecto Benzú: 250.000 años de Historia en la orilla africana del Círculo del Estrecho

Obra extensa sobre el proyecto Benzú, abordado desde diferentes perspectivas

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases

El Abrigo y la Cueva de Benzú; memoria de los trabajos arqueológicos de una década en Ceuta (2002-2012)

Extensa obra que recopila 10 años de trabajos en el Abrigo de Benzú (ceuta)

Aprender no es aburrido

Este proyecto pretende fomentar el interés de los alumnos por el aprendizaje y que adquieran los conceptos mínimos de las distintas materias que componen el currículo de ESO. A la vez, se trabajan las destrezas básicas y las técnicas de estudio a través de juegos. Cada grupo elabora un juego de mesa de preguntas y respuestas y diseñan ellos mismos el tablero y las reglas del juego. Estos juegos se intercambian entre los distintos grupos y se usan para repasar los contenidos de las asignaturas. Además se realiza un juego que consiste en tres pruebas individuales de conocimientos y dos pruebas colectivas de investigación que permiten a cada clase ir sumando puntos. La clase que queda primera gana una excursión. El proyecto ha recibido una gran acogida por parte del alumnado que se ha esforzado por trabajar en equipo, y también ha recibido una valoración muy positiva por parte del profesorado que considera que ha incidido positivamente en los resultados académicos de los alumnos. El proyecto adjunta tres CD-ROM con el juego de Historia del Arte de segundo de Bachillerato, Educación Física de primero de Bachillerato y de memoria visual; y un anexo con la lista de materiales elaborados y fotografías del desarrollo de la experiencia.Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Ordenación AcadémicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES