A5041862524- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- biodegradable polymer synthesis and properties
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Histone Deacetylase Inhibitors Research
- Alzheimer's disease research and treatments
- Spinal Cord Injury Research
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical Acid Research Studies
- Neurotransmitter Receptor Influence on Behavior
- Signaling Pathways in Disease
- Neurological diseases and metabolism
- Muscle Physiology and Disorders
- Multiple Myeloma Research and Treatments
- Neuroscience of respiration and sleep
- Immune Response and Inflammation
- Liver Diseases and Immunity
- Pluripotent Stem Cells Research
- Synthetic Organic Chemistry Methods
- CRISPR and Genetic Engineering
- Pesticide Exposure and Toxicity
Mario Negri Institute for Pharmacological Research
2013-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2022
Center for Neurosciences
2016
Society for Neuroscience
2013
University of Genoa
1997-1998
Freie Universität Berlin
1982
Amyotrophic lateral sclerosis is the most common motor neuron disease and still incurable. The mechanisms leading to selective vulnerability are not known. interplay between neurons astrocytes crucial in outcome of disease. We show that mutant copper-zinc superoxide dismutase (SOD1) overexpression primary astrocyte cultures associated with decreased levels proteins involved secretory pathways. This linked a general reduction total secreted proteins, except for specific enrichment number...
Glutamate‐induced excitotoxicity is suggested to play a central role in the development of amyotrophic lateral sclerosis (ALS), although it still unclear whether represents primary cause cascade leading motor neurone death. We used western blotting, immunocytochemistry and situ hybridization examine expression GLT‐1 transgenic mice carrying mutated (G93A) human copper–zinc superoxide dismutase (TgSOD1 G93A), which closely mimic features ALS. observed progressive decrease immunoreactivity...
In familial and sporadic amyotrophic lateral sclerosis (ALS) in rodent models of the disease, alterations ubiquitin-proteasome system (UPS) may be responsible for accumulation potentially harmful ubiquitinated proteins, leading to motor neuron death. spinal cord transgenic mice expressing ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease constitutive proteasome subunits during disease progression, as assessed by real-time PCR immunohistochemistry. parallel,...
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder involving the selective degeneration of motor neurons. In small proportion patients, ALS caused by mutations in copper/zinc superoxide dismutase (SOD1), and mice overexpressing SOD1(G93A) mutant develop syndrome that closely resembles human disease. Excitotoxicity mediated glutamate AMPA receptors has been suggested to be implicated susceptibility neurons occurring ALS. mice, we found levels GluR2 subunit, which plays...
Cytoskeletal abnormalities with accumulation of ubiquilated inclusions in the anterior horn cells are a pathological hallmark both familial and sporadic amyotrophic lateral sclerosis (ALS) mouse models for ALS. Phosphorylated neurofilaments besides ubiquitin dorfin have been identified as one major components abnormal intracellular perikaryal aggregates. As we recently found that p38 mitogen-activated protein kinase (p38MAPK) colocalized phosphorylated spinal motor neurons SOD1 mutant mice,...
Neuroinflammation is a major hallmark of amyotrophic lateral sclerosis (ALS), which currently untreatable. Several anti-inflammatory compounds have been evaluated in patients and animal models ALS, but proven disappointing part because effective targets not yet identified. Cyclophilin A, also known as peptidylprolyl cis-/trans-isomerase A (PPIA), foldase beneficial intracellularly, extracellularly has detrimental functions. We found that extracellular PPIA mediator neuroinflammation ALS. It...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the motor neuromuscular system leading to complete paralysis and premature death. The multifactorial nature of ALS involves both cell-autonomous non-cell-autonomous processes contributes lack effective therapies, usually targeted single pathogenic mechanism. RNS60, an experimental drug containing oxygenated nanobubbles generated by modified Taylor-Couette-Poiseuille flow with elevated oxygen pressure,...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS other diseases. Its administration been safe well tolerated subjects previous early phase trials.This was II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed definite, probable or laboratory-supported were assigned to...
Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be most effective ALS animal models. The umbilical cord (UC) source highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles Hoechst-33258 transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated...
Abstract Changes in the homeostasis of tumor necrosis factor α (TNFα) have been demonstrated patients and experimental models amyotrophic lateral sclerosis (ALS). However, contribution TNFα to development ALS is still debated. expressed by glia neurons acts through membrane receptors TNFR1 TNFR2, which may opposite effects neurodegeneration. We investigated role its selective motor neuron death vitro vivo . TNFR2 astrocytes neurons, but not TNFR1, was implicated loss primary SOD1‐G93A...
Abstract Glutamate excitotoxicity is implicated in the aetiology of amyotrophic lateral sclerosis (ALS) with impairment glutamate transport into astrocytes a possible cause glutamate‐induced injury to motor neurons. It that mutations Cu/Zn superoxide dismutase (SOD1), responsible for about 20% familial ALS, down‐regulates transporters via oxidative stress. We transfected primary mouse investigate effect FALS‐linked mutant hSOD1 G93A and wild‐type SOD1 (hSOD1 wt ) on uptake system. Using...
The release of glutamic acid and its modulation by 5‐hydroxytryptamine (5‐HT) in the human brain has been investigated synaptosomal preparations from fresh neocortical samples obtained patients undergoing neurosurgery to reach deeply sited tumours. Ca 2+ ‐dependent K + (15 m M )‐evoked overflow glutamate was inhibited 5‐HT a concentration‐dependent manner (EC 50 =2.9 n ; maximal effect ≃50%). inhibition caused antagonized 1 /5‐HT 2 receptor antagonist methiothepin. 1B 1D agonist sumatriptan...
We tested the efficacy of treatment with talampanel in a mutant SOD1 mouse model ALS by measuring intracellular calcium levels and loss spinal motor neurons. intended to mimic clinical study; hence, was started when symptoms were already present. The data compared results similar at presymptomatic stage. Transgenic wild-type mice treated either or vehicle, starting symptomatic stages. density neurons determined physical disector, their level assayed electron microscopically. Results showed...
Efficient application of stem cells to the treatment neurodegenerative diseases requires safe cell tracking follow fate over time in host environment after transplantation. In this work, for first time, fluorescent and biocompatible methyl methacrylate (MMA)-based nanoparticles (fluoNPs) were synthesized through a free-radical co-polymerization process with macromonomer obtained by linking Rhodamine B hydroxyethyl methacrylate. We demonstrate that fluoNPs produced polymerization...
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease caused by the degeneration of motor neurons. The transgenic mouse model carrying human SOD1G93A mutant gene (hSOD1G93A mouse) represents one most reliable and widely used this pathology. In present work, innovative technique matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was applied in study pathological alterations at level small brain regions such as facial trigeminal...