A5004070239- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Epilepsy research and treatment
- Glycogen Storage Diseases and Myoclonus
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neural Engineering
- Chemokine receptors and signaling
- Endoplasmic Reticulum Stress and Disease
- ATP Synthase and ATPases Research
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion Transport and Channel Regulation
- Cytokine Signaling Pathways and Interactions
- Cardiac electrophysiology and arrhythmias
- Synthesis and Biological Evaluation
- Multiple Sclerosis Research Studies
- Neurological diseases and metabolism
- Cancer, Stress, Anesthesia, and Immune Response
University of Perugia
2007-2024
Fondazione Progetto Ematologia
2024
Istituto Neurologico Mediterraneo
2006-2020
Istituto Pasteur
2010-2015
University of Colorado Boulder
2015
Oxford Brookes University
2015
Sapienza University of Rome
2011-2012
Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the parenchyma rendering difficult to eradicate neurosurgery. Efforts identify molecular targets involved invasive behavior of GBM suggested ion channel inhibition as promising therapeutic approach. To determine if Ca2+-dependent K+ KCa3.1 could represent key element for infiltration, human GL-15 cells were xenografted into SCID mice that then treated with specific blocker TRAM-34...
Abstract Misfolding and aggregation of α-synuclein are specific features Parkinson’s disease other neurodegenerative diseases defined as synucleinopathies. progression has been correlated with the formation extracellular release aggregates, well their spread from neuron to neuron. Therapeutic interventions in initial stages require a clear understanding mechanisms by which disrupts physiological synaptic plastic activity basal ganglia. For this reason, we identified two early time points...
Cognitive impairment (CI) is a disabling concomitant of multiple sclerosis (MS) with complex and controversial pathogenesis. The cytokine interleukin-17A (IL-17A) involved in the immune pathogenesis MS, but its possible effects on synaptic function cognition are still largely unexplored. In this study, we show that IL-17A receptor (IL-17RA) highly expressed by hippocampal neurons CA1 area exposure to dose-dependently disrupts long-term potentiation (LTP) through activation p38...
The activation of ion channels is crucial during cell movement, including glioblastoma invasion in the brain parenchyma. In this context, we describe for first time contribution intermediate conductance Ca(2+)-activated K (IK(Ca)) channel activity chemotactic response human lines, primary cultures, and freshly dissociated tissues to CXC chemokine ligand 12 (CXCL12), a whose expression has been correlated with its invasive capacity. We show that blockade IK(Ca) specific inhibitor...
Neuronal nicotinic acetylcholine receptors (nAChRs) containing the α5 subunit modulate nicotine consumption, and human CHRNA5 rs16969968 polymorphism, causing replacement of aspartic acid residue at position 398 with an asparagine (α5DN), has recently been associated increased use tobacco higher incidence lung cancer. We show that in ventral midbrain neurons, is essential for heteromeric nAChR-induced intracellular-free Ca(2+) concentration elevations α5(-/-) mice, a class large-amplitude...
Abstract Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated their growth propagation. In this work we have demonstrated that M2 muscarinic receptors are glioblastoma human specimens cell lines. Moreover, characterized the effects of agonist arecaidine on survival both two different lines (U251 MG U87 ) cultures obtained from biopsies. Cell analysis has strongly decreased proliferation glioma cultures. This effect was dose time dependent. FACS...
We report here the expression and properties of intermediate-conductance Ca(2+)-activated K(+) (IK(Ca)) channel in GL-15 human glioblastoma cell line. Macroscopic IK(Ca) currents on cells displayed a mean amplitude 7.2+/-0.8 pA/pF at 0 mV, day 1 after plating. The current was inhibited by clotrimazole (CTL, IC(50)=257 nM), TRAM-34 (IC(50)=55 charybdotoxin (CTX, IC(50)=10.3 nM). RT-PCR analysis demonstrated mRNA encoding cells. Unitary recorded using inside-out configuration had conductance...
Glioblastoma (GBM) is the most common and aggressive form of brain tumor, characterized by high migratory behavior infiltration in parenchyma which render classic therapeutic approach ineffective. The behaviour GBM cells could be conditioned a number tissue- glioma-derived cytokines growth factors. Although pro-migratory action CXCL12 on vitro vivo recognized, molecular mechanisms involved are not clearly identified. In fact signaling pathways may differ individual glioblastoma integrate...
Ageing is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in function. A genetic study on long-living individuals—who are characterized by delays ageing the onset cardiovascular disease—previously revealed I229V (rs2070325) bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) as a longevity-associated variant (LAV); LAV protein enhanced NO production vasorelaxation through kinase R–like endoplasmic reticulum...
Lafora disease (LD) is a rare progressive disorder caused by mutations in the EPM2A or EPM2B genes, characterized accumulation of bodies, drug-resistant epilepsy, and cognitive decline. To investigate early molecular mechanisms LD, we studied electrophysiological changes dentate gyrus (DG) Epm2aR240X knock-in mouse model at various ages. Electrophysiological recordings measured neuronal membrane properties, epileptic-like activity, epileptic thresholds, synaptic plasticity mice 1, 3, 12...
Some unichiral analogues of 2R,2'S-2-(1'-methyl-2'-pyrrolidinyl)-7-hydroxy-1,4-benzodioxane, a potent and selective α4β2-nAChR partial agonist, were designed by opening dioxane replacing hydroxyl carbon with nitrogen. The resulting 3-pyridyl m-hydroxyphenyl ethers have high α4β2 affinity good subtype selectivity, which get lost if OH is removed from phenyl or the position pyridine nitrogen changed. High selectivity are also attained meta hydroxylating (S)-N-methylprolinol ether...
Abstract Unlike oleate and linoleate, palmitate induced mitochondrial apoptosis in GL15 glioblastoma cells. Decrease membrane potential a subpopulation of mitochondria palmitate‐treated cells was revealed using the 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolylcarbocyanine iodide probe. The diminished ability to reduce tetrazolium salt indicated an impairment function. Up 50% cytochrome c (cyt ) detached from inner released outside cells, whereas no release detected after linoleate...
Energy depletion caused by ischemic brain insults may result in persistent neuronal depolarization accompanied hyper-stimulation of ionotropic glutamate receptors and excitotoxic phenomena, possibly leading to cell death. The use receptor antagonists, such as the AMPARs antagonist Perampanel (PER), might be a pharmacological approach counteract excessive over-activation providing neuroprotective effects. Using electrophysiological molecular analyses, we investigated effect PER against vitro...
Amyloid beta 1-42 (Aβ42) aggregates acutely impair hippocampal long-term potentiation (LTP) of synaptic transmission, and 17β-estradiol is crucial for LTP. We tested whether boosting the synthesis neural-derived (nE2) saves LTP by neurotoxic action Aβ42. Electrophysiological recordings were performed to measure dentate gyrus (DG) in rat slices. Using a pharmacological approach, we ability nE2 counteract impairment caused acute exposure soluble Aβ42 aggregates. was found be required DG under...
Introduction The landscape of epilepsy treatment has undergone a significant transformation with the emergence cannabidiol as potential therapeutic agent. Epidiolex, pharmaceutical formulation highly purified CBD, garnered attention not just for its but also being first cannabis-derived medication to obtain approval from regulatory bodies.