A5085021422- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Supramolecular Self-Assembly in Materials
- Protein Structure and Dynamics
- Prion Diseases and Protein Misfolding
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- S100 Proteins and Annexins
- Advanced Glycation End Products research
- Heat shock proteins research
- Dementia and Cognitive Impairment Research
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Point processes and geometric inequalities
- Science, Research, and Medicine
- Biomedical and Engineering Education
- Metabolomics and Mass Spectrometry Studies
- 14-3-3 protein interactions
- Biochemical and Structural Characterization
- Lipid Membrane Structure and Behavior
- Hydrogels: synthesis, properties, applications
- Proteoglycans and glycosaminoglycans research
- Drug Transport and Resistance Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Biochemical effects in animals
Institute for Research in Biomedicine
2020
MaineGeneral Medical Center
2012-2016
Massachusetts General Hospital
2011-2016
Harvard University
2011-2016
Institute for Bioengineering of Catalonia
2008-2011
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2008-2011
Universitat de Barcelona
2005-2008
École Polytechnique Fédérale de Lausanne
2008
One of the hallmarks Alzheimer's disease is self-aggregation amyloid beta peptide (Abeta) in extracellular fibrils. Among different forms Abeta, 42-residue fragment (Abeta1-42) readily self-associates and nucleation centers from where fibrils can quickly grow. The strong tendency Abeta1-42 to aggregate one reasons for scarcity data on its fibril formation process. We have used atomic force microscopy (AFM) visualize liquid environment fibrillogenesis synthetic hydrophilic hydrophobic...
Recent experimental evidence points to intermediates populated during the process of amyloid fibril formation as toxic moieties primarily responsible for development increasingly common disorders such Alzheimer's disease and type II diabetes. We describe here application a pulse-labeling hydrogen-deuterium (HD) exchange strategy monitored by mass spectrometry (MS) NMR spectroscopy (NMR) characterize aggregation an SH3 domain under 2 different conditions, both which ultimately lead...
Abstract Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which thought to drive amyloid plaque formation brain these patients. Little known however whether ageing, major risk factor for sporadic AD, affects beta‐peptide (Aβ) generation as well. Here we demonstrate that secretion Aβ enhanced an vitro model neuronal correlating with increase γ‐secretase complex formation. Moreover found peroxynitrite (ONOO − ), produced...
The histopathological hallmarks of Alzheimer disease are the self-aggregation amyloid beta peptide (Abeta) in extracellular fibrils and formation intraneuronal Tau filaments, but a convincing mechanism connecting both processes has yet to be provided. Here we show that endogenous polysaccharide chondroitin sulfate B (CSB) promotes fibrillar structures 42-residue fragment, Abeta(1-42). Atomic force microscopy visualization, thioflavin T fluorescence, CD measurements, cell viability assays...
Highlights•The head contains nicastrin ectodomain and overhangs a solute-accessible cavity in base•The base has central channel lateral cleft (putative substrate docking site)•Inhibitors close the rotate head, blocking accessSummaryPresenilin-mediated endoproteolysis of transmembrane proteins plays key role physiological signaling pathogenesis Alzheimer disease some cancers. Numerous inhibitors have been found via library screens, but their structural mechanisms remain unknown. We used...
The structure and function of the γ-secretase proteases are vast interest because their critical roles in cellular disease processes. We established a novel purification protocol for complex that involves conformation complex-specific nanobody, yielding highly pure active enzyme. Using single particle electron microscopy, we analyzed its conformational variability. Under steady state conditions adopts three major conformations, which different overall compactness relative position nicastrin...
Synaptic loss strongly correlates with memory deterioration. Local accumulation of amyloid β (Aβ) peptide, and neurotoxic Aβ42 in particular, due to abnormal neuronal activity may underlie synaptic dysfunction, neurodegeneration, impairments. To gain an insight into molecular events underlying activity-regulated Aβ production at the synapse, we explored functional outcomes newly discovered calcium-dependent interaction between Alzheimer’s disease-associated presenilin 1 (PS1)/γ-secretase...
One mechanism leading to neurodegeneration during Alzheimers Disease (AD) is amyloid β peptide (Aβ)- induced neurotoxicity. Among the factors proposed potentiate Aβ toxicity its covalent modification through carbohydrate- derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate neurotoxic effect of primary neuronal cultures. Pretreatment...
Amyloid-β protein (Aβ) aggregation into amyloid fibrils is central to the origin and development of Alzheimer's disease (AD), yet this highly complex process poorly understood at molecular level. Extensive studies have shown that Aβ fibril growth occurs through elongation, whereby soluble molecules add ends. Nevertheless, morphology strongly depends on conditions. For example, high ionic strength, laterally associate bundles. To further study mechanisms leading growth, we developed a...
Abstract The Institute for Research in Biomedicine (IRB Barcelona) is a world‐class research center devoted to understanding fundamental questions about human health and disease. In addition conducting multidisciplinary of excellence, IRB Barcelona committed maintaining an open dialogue with the public its work, fostering scientific vocations promoting culture society. this regard, institute has several engagement science education initiatives reach these goals. article, we highlight two...
G-secretase is the complex responsible for final step in processing of amyloid precursor protein (APP), liberating amyloid-b (Ab) peptides various lengths. Longer Ab species are implicated pathological cascade leading to Alzheimer's disease (AD). Presenilin1 (PS1) catalytic subunit g-secretase complex. More than 160 mutations PS1 have been linked familial AD (fAD). We previously shown that several fAD lead a change conformation, affect alignment with APP substrate, and alter precision...
Synaptic dysfunction is a key feature of Alzheimer's disease and closely correlates with memory impairment. Activity-dependent production beta-amyloid, targeted accumulation beta-amyloid oligomers at the synapse have been reported. Consistently, we recently reported that neuronal activation causes an increase in presenilin 1 (PS1)- precursor protein interaction secretion. However, event(s) protein(s) are involved synaptic remain largely unknown. Therefore, attempted to search for...