A5086345183- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Glioma Diagnosis and Treatment
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Brain Tumor Detection and Classification
- Biochemical effects in animals
- Cell Image Analysis Techniques
- Radiomics and Machine Learning in Medical Imaging
- Parkinson's Disease Mechanisms and Treatments
- Cassava research and cyanide
- Sirtuins and Resveratrol in Medicine
Universidad Autónoma de Madrid
2016-2025
Centro de Biología Molecular Severo Ochoa
2013-2025
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2024
Instituto de Salud Carlos III
2024
Consejo Superior de Investigaciones Científicas
2002
Mitochondrial anomalies have been previously reported in patients′ brain and peripheral tissue, suggesting their relevance sporadic Alzheimer's disease (AD). The present work evaluates mitochondrial function recycling human fibroblasts biopsies. Functional studies using skin showed slower membrane potential recovery after a insult together with alterations lysosomes autophagy, accompanied by an increase of oxidized ubiquitinated proteins. Impairment mitophagy has proven these cells due to...
Sporadic Alzheimer’s disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction a major feature pathology, which might be one the early events that trigger downstream principal events. Here, we show multiple genes control mitochondrial homeostasis, including fission fusion, are downregulated in patients. Additionally, demonstrate some these dysregulations, such as diminished DLP1 levels its localization, well reduced STOML2 MFN2 fusion protein...
Almost a 20% of the residues tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on consequences for being phosphoprotein. We will focus serine/threonine phosphorylation. It be discussed that, depending modified residue in molecule, phosphorylation could protective, processes like hibernation, or toxic development those diseases known as tauopathies, which characterized by an hyperphosphorylation aggregation tau.
Familial Alzheimer's disease is clearly related with the accumulation of amyloid-beta and its deleterious effect on mitochondrial function well established. Anomalies in autophagy have also been described these patients. In present work, functional analyses performed to study recycling process patient-derived fibroblasts neurons from induced pluripotent stem cells harboring presenilin 1 mutation A246E. Mitophagy impairment was observed due a diminished degradation phase associated lysosomal...
TAU is expressed in the less aggressive gliomas where it impairs mesenchymal transdifferentiation of tumor cells and normalizes vasculature.
Abstract Tauopathies, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration with Tau pathology (FTLD-tau), are a group of neurodegenerative disorders characterized by hyperphosphorylation. Post-translational modifications such as phosphorylation truncation have been demonstrated to be an essential step in the molecular pathogenesis these tauopathies. In this work, we demonstrate existence new, human-specific truncated form generated intron 12 retention human neuroblastoma...
Tauopathies comprise a range of neurodegenerative conditions characterized by the aberrant accumulation tau protein clumps in brain. These aggregates are formed different splicing isoforms. Here, we analyzed role specific intron-derived peptide called W-Tau on polymerization–depolymerization filaments. This originates from new isoform protein, named W-Tau, which is due to retention intron 12. AlphaFold3 (AF3)-based silico investigations suggested that interacts with monomers. Our vitro...
Mitochondrial alterations and oxidative stress are common features of Alzheimer's disease brain peripheral tissues. Moreover, mitochondrial recycling process by autophagy has been found altered in the sporadic form disease. However, contribution main proteins involved this pathology such as amyloid-β protein precursor (AβPP) tau needs to be achieved. With aim, human unmodified fibroblasts were transduced with lentivectors encoding APP Tau treated CCCP study mitophagy process. Both AβPP...
Autophagy is mainly a cellular recycling process that promotes survival, but it can also cause cell death if injury persists. The role of mitophagy in tumorigenesis remains uncertain. Other types, such as apoptosis or necrosis, are often altered during tumor development and therefore not ideal targets to generate efficient antitumor therapies. We have used the system linamarase/linamarin/glucose oxidase (lis/lin/GO) eliminate cells. This therapeutic strategy based on combination cyanide...
Alzheimer's disease (AD) and other tauopathies are histopathologically characterized by tau aggregation, along with a chronic inflammatory response driven microglia. Over the past few years, role of microglia in AD has been studied mainly relation to amyloid-β (Aβ) pathology. Consequently, there is substantial knowledge gap concerning molecular mechanisms involved tau-mediated toxicity neuroinflammation, thus hindering development therapeutic strategies. We previously demonstrated that...
BackgroundTau is a microtubule-binding protein encoded by the MAPT gene. Tau essential for several physiological functions and associated with pathological processes, including Alzheimer's disease (AD). Six tau isoforms are typically described in central nervous system, but current research paints more diverse landscape nuanced balance between isoforms. Recent work has generated intron 11 12 retention. This adds to that evidence, proving existence of transcripts retaining 3. Our aim...
A continuous normal function of olfactory ensheathing glia (OEG) is to promote axonal regeneration from the neuroepithelium brain, and their neuroregenerative potential in other CNS sites such as injured spinal cord has been studied for over a decade. However, human OEG are difficult obtain large amounts directly tissues, derived primary cultures have limited duplication capacity. Thus, although auto-transplantation may be an obvious option initial proof-of-concept trials, alternatives must...
Reversible immortalization holds great potential for primary tissue expansion to develop cell-based therapies as well basic research. Human olfactory ensheathing glia (hOEG) are promising candidates treating spinal cord injury and studying extrinsic neuroregenerative mechanisms. We used lentivectors with Cre/loxP technology achieve reversible gene transfer of BMI1, SV40 large T antigen (TAg), a short hairpin RNA against p53 (shp53), the catalytic subunit telomerase (TERT) in cultures hOEG...
Tau is a cytoskeletal protein present mainly in the neurons of vertebrates. By comparing sequence tau molecule among different vertebrates, it was found that variability N‐terminal higher than C‐terminal region. The region involved binding to cellular membranes, whereas contains microtubule‐binding sites. We have compared Syrian hamster with sequences other hibernating and nonhibernating rodents investigated how differences could affect phosphorylation level cell membranes. also describe...
Olfactory ensheathing glia (OEG) cells are known to facilitate repair following axotomy of adult neurons, although the molecular mechanisms involved not fully understood. We previously identified plasminogen activator inhibitor-1 (PAI-1), proteinase-activated receptor-1 (PAR-1), and thrombomodulin (TM) as candidates regulate rat OEG-dependent axonal regeneration. In this study, we have validated involvement these proteins in promoting regeneration by immortalized human OEGs. studied effect...
The understanding of the mechanisms cell-death execution and role that they play in different diseases opens new therapeutic strategies. Currently, increasing evidence indicates autophagy is a frequent mechanism, so question arises: Could stimulation be considered an antitumor therapy? Several inducers have been used as anticancer agents and, although complete tumor eradication has not demonstrated, effect very promising. We recently demonstrated strong mediated by combined generation...
Abstract We present here a suicide therapy against malignant gliomas based on the transfer to tumor cells of gene encoding β-glucosidase, linamarase (lis), which in presence innocuous substrate linamarin (lin) produces cyanide, blocking mitochondrial respiratory chain. Dog glioma carrying lis are thus sensitive lin (IC50 250 μg/mL at 48 hours) and cell death is accompanied by fission ATP depletion. The combination lis/lin with an otherwise nontoxic level glucose oxidase (GO) enhances...
Ensheathing glia have been demonstrated to neuroregenerative properties but this cell type from human sources has not extensively studied because tissue samples are easily obtained, primary cultures slow growing, and lines available. We previously isolated immortalized ensheathing by gene transfer of BMI1 telomerase catalytic subunit into derived olfactory bulbs an elderly cadaver donor. These cells escape the replicative senescence characteristic while conserving antigenic glia, their low...