A5079904740- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Connective tissue disorders research
- Congenital heart defects research
- Computational Drug Discovery Methods
- Liver Disease Diagnosis and Treatment
- Tissue Engineering and Regenerative Medicine
- Cardiac Valve Diseases and Treatments
- Nuclear Receptors and Signaling
- Receptor Mechanisms and Signaling
- Craniofacial Disorders and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Synthesis and biological activity
- Neurogenetic and Muscular Disorders Research
- Ovarian function and disorders
- RNA Interference and Gene Delivery
- Tumors and Oncological Cases
- Patient-Provider Communication in Healthcare
- Menopause: Health Impacts and Treatments
- Cardiac Fibrosis and Remodeling
- Ocular Oncology and Treatments
Pontificia Universidad Católica de Chile
2010-2024
University of Cambridge
2015-2022
Wellcome/MRC Cambridge Stem Cell Institute
2016-2022
Medical Research Council
2018
McLaren Health Care
2016
Instituto de Investigación Sanitaria La Fe
2012-2016
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2012-2016
Fundación Chile
2013-2014
Universidad de Murcia
1993
Growing evidence indicates that Wingless-type (Wnt) signaling plays an important role in the maturation of central nervous system. We report here family member 5A (Wnt-5a) is expressed early development and stimulates dendrite spine morphogenesis, inducing de novo formation spines increasing size preexisting ones hippocampal neurons. Wnt-5a increased intracellular calcium concentration dendritic processes amplitude NMDA spontaneous miniature currents. Acute application field excitatory...
Contextual memory formation relies on the induction of new genes in hippocampus. A polymorphism promoter transcription factor XBP1 was identified as a risk for Alzheimer's disease and bipolar disorders. is major regulator unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using phenotypic screen, we uncovered an unexpected function cognition behavior. Mice lacking nervous system showed specific impairment contextual long-term potentiation (LTP),...
We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer's disease. Biological screening performed in vitro and Escherichia coli cells has shown that these exhibit potent inhibitory activities against human acetylcholinesterase, butyrylcholinesterase, BACE-1, dual Aβ42 tau antiaggregating activity, brain permeability. Ex vivo studies with the leads (+)- (-)-7e slices C57bl6 mice revealed they efficiently protect Aβ-induced synaptic dysfunction,...
To define whether anti-ribosomal P (anti-P) autoantibodies from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) impair the function of hippocampal neurons that express neuronal surface antigen (NSPA) when accessing brain via circulating blood.We used anti-P antibodies NPSLE and rabbit-generated anti-NSPA antibodies. Primary mice were analyzed to determine antibody cell binding (double immunofluorescence), intracellular calcium variations (Fura 2 AM), apoptosis (caspase 3...
Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are key factor synaptic impairment and spatial memory decline associated with neuronal dysfunction. This includes failure loss of proteins that contribute to AD progression. Interestingly, use natural compounds an emergent conceptual strategy search for drugs therapeutic potentials treating disorders. In present study, we report andrographolide (ANDRO), labdane diterpene extracted from Andrographis...
Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods complex, lack robustness do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible knockdown or knockout (sOPTiKD sOPTiKO) platforms. These based on genetic engineering human genomic safe harbors combined with an improved tetracycline-inducible system CRISPR/Cas9 technology. We...
The early stages of Alzheimer's disease are characterised by impaired synaptic plasticity and synapse loss. Here, we show that amyloid-β oligomers (AβOs) activate the c-Abl kinase in dendritic spines cultured hippocampal neurons activity is required for AβOs-induced We also EphA4 receptor tyrosine upstream activation AβOs. phosphorylation (activation) increased synaptoneurosomes exposed to AβOs, Alzheimer-transgenic mice brain. do not detect EphA4-knockout More interestingly, demonstrate...
Objective To assess whether autoantibodies against ribosomal P (anti‐P), which are possibly pathogenic in neuropsychiatric systemic lupus erythematosus (NPSLE), alter glutamatergic synaptic transmission and to what extent the cross‐reacting neuronal surface antigen (NSPA) is involved. Methods We analyzed long‐term potentiation (LTP) mediated by AMPA receptor (AMPAR) N ‐methyl‐ d ‐aspartate (NMDAR) field excitatory postsynaptic potential (EPSP) at CA3–CA1 synapse. AMPAR activation patch‐clamp...
There were two errors published in Development 142, 1528-1541.LM cells seeded at a density of 2.5×104/cm2. To generate EPI-CFs, epicardial differentiated CDM-PVA with VEGF-B (and FGF2). Although the are minor and do not affect science presented, they important if others wish to replicate protocol.The authors apologise readers for these mistakes.
Genome-wide association studies have identified multiple novel genomic loci associated with vascular diseases. Many of these are common non-coding variants that affect the expression disease-relevant genes within coronary cells. To identify such on a genome-wide level, we performed deep transcriptomic analysis genotyped primary human artery smooth muscle cells (HCASMCs) and endothelial (HCAECs) from same subjects, including splicing Quantitative Trait Loci (sQTL), allele-specific (ASE),...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ) accumulation and synaptic alterations. Previous studies indicated that hyperforin, component the St John's Wort, prevents Aβ neurotoxicity some behavioral impairments in rat model AD. In this study we examined ability tetrahydrohyperforin (IDN5607), stable hyperforin derivative, to prevent deficit impairment an vivo double transgenic...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive abilities, accumulation the amyloid-β peptide (Aβ), increase oxidative stress, and synaptic alterations. The scavenging reacti
The neural crest (NC) is a transient multipotent cell population present during embryonic development. NC can give rise to multiple types and involved in number of different diseases. Therefore, the development new strategies model vitro enables investigations into mechanisms disease. In this study, we report simple efficient protocol differentiate human pluripotent stem cells (HPSC) using chemically defined media, with basic fibroblast growth factor 2 (FGF2) transforming factor-β inhibitor...
Abstract Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. However, because iECs iSMCs are not derived from an intact blood vessel, they represent immature phenotype. Hemodynamics heterotypic cell:cell communication play important roles in cell phenotypic modulation. Here we tested the hypothesis that hemodynamic exposure of coculture with induces vivo-like were cocultured under region-specific flow...
The concept of the ovarian continuum can be understood as a process that occurs during woman's lifetime and begins intrauterine life with fertilization. Women start their reproductive years approximately five hundred thousand follicles containing oocytes, which only around will released ovulation. Ovulation has been recognized an event linked reproduction; however, recent evidence supports role ovulation sign health. use biomarkers help women recognize enables them to identify health status....
A cohort of 141 males (18-80 yo, 42.9±12.9) strongly suspected being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) ≥150 mg/dL Non-Insulin (NIR) SSPG 3.0 ng/mL. Two out three turned to be IR, while around one in four HYPOG. Contingency analysis indicated a significant interdependence...
Abstract Somatic cells can be reprogrammed to induced pluripotent stem (iPS) by ectopic expression of the four factors Oct4, Klf4, Sox2, and Myc. Here, we investigated role Gata4 in reprogramming process present evidence for a negative this family transcription induction pluripotency. Coexpression with Sox2 or without Myc mouse embryonic fibroblasts greatly impaired endogenous Nanog expression. The lack upregulation was associated blockade transition from initiation phase full state...