A5067836916- Adenosine and Purinergic Signaling
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenetic and Muscular Disorders Research
- Neurological Complications and Syndromes
- Nerve injury and regeneration
- Mast cells and histamine
- Neurogenesis and neuroplasticity mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Immune Response and Inflammation
- Multiple Sclerosis Research Studies
- S100 Proteins and Annexins
- Cellular transport and secretion
- Restless Legs Syndrome Research
- Parkinson's Disease Mechanisms and Treatments
- Connexins and lens biology
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Olfactory and Sensory Function Studies
- Polyomavirus and related diseases
- Neuropeptides and Animal Physiology
- Mitochondrial Function and Pathology
Fondazione Santa Lucia
2014-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2003-2024
Institute of Cell Biology and Neurobiology
2013-2016
Institute of Neurobiology and Molecular Medicine
2011
University of Rome Tor Vergata
2003-2007
Inserm
1994
Abstract In recent years there has been an increasing awareness on the role of P2X7 receptor for extracellular ATP in modulating physiopathological mechanisms CNS. particular, was shown to be implicated neuropsychiatry, chronic pain, neurodegeneration, neuroinflammation. Remarkably, a "gene modifier" amyotrophic lateral sclerosis (ALS): is up-regulated spinal cord microglia human and rat at advanced stages disease; vitro, activation exacerbates pro-inflammatory responses ALS-microglia, as...
Understanding the means by which microglia self-regulate neuroinflammatory response helps modulating their reaction during neurodegeneration. In amyotrophic lateral sclerosis (ALS), classical NF-κB pathway is related to persistent activation and motor neuron injury; however, mechanisms of negative control activity remain unexplored. One major players in termination ubiquitin-editing enzyme A20, has recognized anti-inflammatory functions. Lately, microRNAs are emerging as potent fine-tuners...
Abstract To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized expression and functional activity P2 cultured rat progenitors investigated effects ATP its breakdown products on migration proliferation this immature glial cell population. Using Western blot analysis, show that express several P2X (P2X 1,2,3,4,7 ) P2Y (P2Y 1,2,4 receptors. Intracellular Ca 2+ recording by Fura‐2 video imaging allowed to determine rank potency order agonists...
Adenosine 5′-triphosphate outflow increases after an ischemic insult in the brain and may induce expression of P2X 7 receptors resting microglia, determining its modification into activated state. To assess effects receptor blockade preventing microglia activation ameliorating damage neurological impairment, we delivered P2 unselective antagonist Reactive Blue 2 to rats middle cerebral artery occlusion. In sham-operated animals, devoid damage, double immunofluorescence verified absence...
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by selective degeneration of upper and lower motoneurons. The primary triggers for motoneuron are still unknown, but inflammation considered an important contributing factor. P2X7 receptor key player in microglia response to toxic insults was previously shown increase pro-inflammatory actions SOD1-G93A ALS microglia. We therefore hypothesized that lack could modify disease features the mice. Hetero-...
Autophagy and inflammation play determinant roles in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), an adult-onset neurodegenerative disease characterized by deterioration final loss upper lower motor neurons priming microglia to sustain neuroinflammation a vicious cycle neurodegeneration. Given that extracellular ATP through P2X7 receptor constitutes neuron-to-microglia alarm signal implicated ALS, affects autophagy immune cells, we have investigated if can be directly triggered...
Although Multiple Sclerosis (MS) is regarded as a white matter disease, the incidence of demyelination and axonal injury prominent also in gray matter. In MS, extracellular adenosine triphosphate (ATP) an important mediator central nervous system pathology via its ability to cause oligodendrocyte excitotoxicity. We have analyzed distribution pattern all ionotropic P2X metabotropic P2Y receptors for ATP postmortem samples cerebral cortex from healthy human subjects well MS patients. focus...
In the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple (MS) is consequence of an intricate interplay orchestrated by various cell phenotypes. Among molecular cues having a role in this process, extracellular nucleotides are responsible for intercellular communication propagation inflammatory stimuli. This occurs binding to several receptor subtypes, defined P2X/P2Y, which widespread different tissues simultaneously localized on cells....
Multiple sclerosis (MS) is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R) known be abundantly expressed on cells of hematopoietic lineage nervous system, we further investigated its phenotypic expression in MS experimental autoimmune encephalomyelitis conditions. By quantitative reverse transcription polymerase chain reaction flow cytometry, analyzed P2X7R human mononuclear peripheral...
Amyotrophic lateral sclerosis (ALS) is a disease with strong neuroinflammatory component sustained by activated microglia contributing to motoneuron death. However, how successfully balance neuroprotective versus neurotoxic actions the use of antinflammatory agents still under scrutiny. We have recently shown that antihistamine clemastine, an FDA-approved drug, can influence M1/M2 switch occurring in SOD1-G93A ALS microglia.Here, we chronically treated female mice evaluated progression and...
Here, we report on the identification of Itga7-expressing muscle-resident glial cells activated by loss neuromuscular junction (NMJ) integrity. Gene expression analysis at bulk and single-cell level revealed that these are distinct from muscle satellite cells. We show a selective activation expansion Itga7+ occur in response to nerve lesion. Upon activation, glial-derived progenies expressed neurotrophic genes, including growth factor receptor, which enables their isolation FACS. also genes...
Immunometabolism investigates the intricate relationship between immune system and cellular metabolism. This study delves into consequences of mitochondrial frataxin (FXN) depletion, primary cause Friedreich’s ataxia (FRDA), a debilitating neurodegenerative condition characterized by impaired coordination muscle control. By using single-cell RNA sequencing, we have identified distinct clusters within cerebellum an FRDA mouse model, emphasizing significant loss in homeostatic response...
Several mutations in the SOD1 gene encoding for antioxidant enzyme Superoxide Dismutase 1, are associated with amyotrophic lateral sclerosis, a rare and devastating disease characterized by motor neuron degeneration patients' death within 2–5 years from diagnosis. Motor loss related symptomatology manifest mostly adult life and, to date, there is still gap of knowledge on precise cellular molecular events preceding neurodegeneration. To deepen our awareness early phases disease, we leveraged...
Our work aimed to provide a topographical analysis of all known ionotropic P2X(1-7) and metabotropic P2Y(1,2,4,6,11-14) receptors that are present in vivo at the protein level basal ganglia nuclei particularly rat brain slices from striatum substantia nigra. By immunohistochemistry-confocal Western blotting techniques, we show that, with exception P2Y(11,13) receptors, other subtypes specifically expressed these areas different amounts, ratings low (P2X(5,6) P2Y(1,6,14) striatum), medium...
Background and Purpose Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by the degeneration of upper lower motor neurons, progressive wasting paralysis voluntary muscles is currently incurable. Although considered to be pure neuron disease, increasing evidence indicates that sole protection neurons single targeted drug not sufficient improve pathological phenotype. We therefore evaluated therapeutic potential multi‐target used treatment coronary artery...