A5002363041- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Alzheimer's disease research and treatments
- Circular RNAs in diseases
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Lipid Membrane Structure and Behavior
- Adenosine and Purinergic Signaling
- Cannabis and Cannabinoid Research
- Adipokines, Inflammation, and Metabolic Diseases
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Neuroscience of respiration and sleep
- Apelin-related biomedical research
- Planarian Biology and Electrostimulation
- Inflammation biomarkers and pathways
- MXene and MAX Phase Materials
- Receptor Mechanisms and Signaling
- Caveolin-1 and cellular processes
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Human-Animal Interaction Studies
- Sleep and Wakefulness Research
Neuroscience Institute
2015-2023
University of Milan
2017
National Research Council
2016
Vita-Salute San Raffaele University
2006-2013
Humanitas University
2013
San Raffaele University of Rome
2011
Italian Institute of Technology
2011
Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action reactive causing defects not fully understood. In this study, we show that inflammatory produce extracellular vesicles (EVs) enriched a set miRNAs regulate expression key proteins. Among them, miR-146a-5p, microglia-specific miRNA present hippocampal neurons, controls...
ABSTRACT Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central the biogenesis, content, function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes EVs, International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 Baltimore, Maryland, USA, bringing together key opinion leaders hands‐on researchers who were selected basis submitted...
Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs), which are potent mediators intercellular communication between microenvironment. We previously showed that EVs produced under stimulation (ATP-EVs) propagate a robust inflammatory reaction astrocytes in vitro mice with subclinical neuroinflammation (1). However, proteome released upon has not yet been elucidated. In this study we applied label free proteomic approach...
Abstract Synaptic dysfunction is an early mechanism in Alzheimer’s disease that involves progressively larger areas of the brain over time. However, how it starts and propagates unknown. Here we show amyloid-β released by microglia association with large extracellular vesicles (Aβ-EVs) alters dendritic spine morphology vitro, at site neuron interaction, impairs synaptic plasticity both vitro vivo entorhinal cortex–dentate gyrus circuitry. One hour after Aβ-EV injection into mouse cortex,...
Growing evidence indicates that sphingosine-1-P (S1P) upregulates glutamate secretion in hippocampal neurons. However, the molecular mechanisms through which S1P enhances excitatory activity remain largely undefined. The aim of this study was to identify presynaptic targets action controlling exocytosis. Confocal analysis rat neurons showed applied at nanomolar concentration alters distribution Synapsin I (SynI), a phosphoprotein controls availability synaptic vesicles for induced SynI...
Astrocytes are the brain nonnerve cells that competent for gliosecretion, i.e., expression and regulated exocytosis of clear dense-core vesicles (DCVs). We investigated whether astrocyte DCVs is governed by RE-1–silencing transcription factor (REST)/neuron-restrictive silencer (NRSF), repressor orchestrates nerve cell differentiation. Rat cultures exhibited high levels REST expressed neither nor their markers (granins, peptides, membrane proteins). Transfection a dominant-negative construct...
Extracellular vesicles (EVs) are spherical membrane structures released by most cells. These highly conserved mediators of intercellular communication carry proteins, lipids, and nucleic acids, transfer these cellular components between cells different mechanisms, such as endocytosis, macropinocytosis, or fusion. However, the temporal spatial dynamics vesicle—cell interactions still remain largely unexplored. Here we used optical tweezers to drive single EVs produced microglial onto surface...
In the substantia nigra of human brain, neuromelanin (NM) released by degenerating neurons can activate microglia with consequent neurodegeneration, typical Parkinson's disease (PD). Synthetic analogues NM were prepared to develop a PD model reproducing neuropathological conditions disease. Soluble melanin–protein conjugates obtained melanization fibrillated β-lactoglobulin (fLG). The melanic portion contains either eumelanic (EufLG) or mixed eumelanic/pheomelanic composition (PheofLG),...
SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation these targets.The 3'-UTRs brain compared to other tissues predict important roles for miRNAs.Supporting this notion, we found miRNAs co-evolved their target transcripts, non-coding pseudogenes miRNA recognition elements...
Expression of neurosecretion by nerve cells requires the levels transcription repressor element-1 silencing factor (REST) to be very low. However, when high-REST clones PC12 cells, defective neurosecretion, were fused other high-REST, non-neurosecretory some was recovered. To clarify mechanism this recovery, we with human lymphocytes. A cytogenetic analysis revealed all hybrid that recovered contain a fragment chromosome 11 including gene encoding BHC80, protein one complexes mediate REST...
We have uncovered a novel role for astrocytes-derived extracellular vesicles (EVs) in controlling intraneuronal Ca2+ concentration ([Ca2+]i) and identified transglutaminase-2 (TG2) as surface-cargo of EVs. Incubation hippocampal neurons with primed astrocyte-derived EVs led to an increase [Ca2+]i, unlike from TG2-knockout astrocytes. Exposure or brain slices TG2 promoted [Ca2+]i rise, which was reversible upon removal dependent on influx through the plasma membrane. Patch-clamp calcium...
Trehalose is a nonreducing disaccharide that has recently attracted much attention because of its ability to inhibit protein aggregation, induce autophagy, and protect against dissections strokes. In vertebrates, the biosynthesis trehalose was long considered absent due lack annotated genes involved in this process. contrast, trehalase (TreH), which an enzyme required for cleavage trehalose, known be conserved expressed. Here, we show present as endogenous metabolite rodent hippocampus. We...
Studies carried out by immunofluorescence, patch‐clamping and FM dye fluorescence consistently showed that the Ca 2+ ‐induced exocytosis of enlargeosomes, specific vesicles expressed many cell types, is strongly reinforced pre‐treatment cells with genistein, a wide spectrum blocker tyrosine kinases, which also induces additional effects. Various other blockers however, were ineffective, same occurred drugs mimicking most rapid, non‐tyrosine kinase‐dependent effects genistein. The...
Astrocytes are the brain nonnerve cells that competent for gliosecretion, i.e., expression and regulated exocytosis of clear dense-core vesicles (DCVs). We investigated whether astrocyte DCVs is governed by RE-1-silencing transcription factor (REST)/neuron-restrictive silencer factor, repressor orchestrates nerve cell differentiation. Rat cultures exhibited high levels REST expressed neither nor their markers (granins, peptides, membrane proteins). Transfection dominant-negative construct...
Abstract Background Synaptic dysfunction is an early mechanism in Alzheimer’s disease (AD) which involves progressively larger areas of the brain over time. However, how it starts and propagates unknown. We hypothesised that large extracellular vesicles (EVs) released by microglia may be responsible for these events AD. Method Large EVs carrying Aβ peptides (Aβ‐EVs) were obtained from primary exposed to 42. Optical manipulation was combined with time lapse imaging study EV‐neuron...