A5064344624- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Cholinesterase and Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Wnt/β-catenin signaling in development and cancer
- Biochemical Acid Research Studies
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
- Nerve injury and regeneration
- Pain Management and Placebo Effect
- Autophagy in Disease and Therapy
- S100 Proteins and Annexins
- biodegradable polymer synthesis and properties
- Neuroscience and Neuropharmacology Research
- Synthetic Organic Chemistry Methods
- Trace Elements in Health
- Neurogenesis and neuroplasticity mechanisms
Istituto di Farmacologia Traslazionale
2015-2024
University of Salerno
2024
National Research Council
2013-2023
Consorzio Roma Ricerche
2021
Valencian Infertility Institute
2020
Fondazione Santa Lucia
2007-2018
Istituti di Ricovero e Cura a Carattere Scientifico
2006-2016
University of Rome Tor Vergata
2004-2015
Dulbecco Telethon Institute
2004
Institute of Neurobiology and Molecular Medicine
1995-2003
Recent studies suggest that the toxicity of familial amyotrophic lateral sclerosis mutant Cu, Zn superoxide dismutase (SOD1) arises from its selective recruitment to mitochondria. Here we demonstrate each 12 different ALS-mutant SOD1s with widely differing biophysical properties are associated mitochondria motoneuronal cells a much greater extent than wild-type SOD1, and this effect may depend on oxidation Cys residues. We further SOD1 proteins tend form cross-linked oligomers their presence...
Abstract Inflammation and oxidative stress are thought to play determinant roles in the pathogenesis of amyotrophic lateral sclerosis (ALS). Degenerating motor neurons produce signals that activate microglia release reactive oxygen species (ROS) proinflammatory cytokines, resulting a vicious cycle neurodegeneration. The ALS-causing mutant protein Cu+/Zn+ superoxide dismutase SOD1-G93A directly enhances activity main ROS-producing enzyme microglia, NADPH oxidase 2 (NOX2), well-known player...
A common feature of non-coding repeat expansion disorders is the accumulation RNA repeats as foci in nucleus and/or cytoplasm affected cells. These can be toxic by sequestering RNA-binding proteins, thus affecting various steps post-transcriptional gene regulation. However, precise step that C9orf72 GGGGCC (G4C2) expansion, major genetic cause Amyotrophic Lateral Sclerosis, still poorly defined. In this work, we set out to characterise these mechanisms identifying binding proteins....
Macroautophagy/autophagy is an essential process for cellular survival and implicated in many diseases. A critical step autophagy the transport of transcription factor TFEB from cytosol into nucleus, through nuclear pore (NP) by KPNB1/importinβ1. In C9orf72 subtype amyotrophic lateral sclerosis-frontotemporal lobar degeneration (ALS-FTD), hexanucleotide (G4C2)RNA expansion (HRE) disrupts nucleocytoplasmic TFEB, compromising autophagy. Here we show that a molecular chaperone, SIGMAR1/Sigma-1...
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction cellular molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects disease. Niclosamide, an anthelminthic drug listed as essential medicine, has been repurposed clinical trials different diseases due to its anti-inflammatory anti-fibrotic properties....
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of lower and upper motoneurons. The pathology imputable in ∼2% cases to mutations ubiquitous enzyme Cu, Zn superoxide dismutase (SOD1). Common theories explain pathogenic mechanisms ALS include activation microglia, responsible for release proinflammatory factors. However, how mutant SOD1 affects microglial subsequently injures neurons still unclear. Considering that...
Vulnerability of motoneurons in amyotrophic lateral sclerosis (ALS) arises from a combination several mechanisms, including protein misfolding and aggregation, mitochondrial dysfunction oxidative damage. Protein aggregates are found models for ALS linked to mutation the gene coding Cu,Zn superoxide dismutase (SOD1) patients as well. Aggregation mutant SOD1 cytoplasm and/or into mitochondria has been repeatedly proposed main culprit degeneration motoneurons. It is, however, still debated...
cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at edge subunit interface. It also binds Cu2–Zn2 and Zn2–Zn2 forms hSOD1. Cisplatin inhibits aggregation demetalated hSOD1, it further dissolve monomerize hSOD1 oligomers vitro cell, thus indicating its potential as leading compound for amyotrophic lateral sclerosis.
Increasing evidence indicates that the accumulation and aggregation of mutant Cu,Zn superoxide dismutase (mutSOD1) in spinal cord mitochondria is implicated pathogenesis familial amyotrophic lateral sclerosis (FALS). Although mechanisms underlying this effect are only partially understood, a deficit import mechanism mutSOD1 and/or its folding maturation inside likely involved. To investigate issue, we overexpressed mitochondria-targeted wild-type mutSOD1s neuronal cell lines....
TAR DNA-binding protein 43 (TDP-43) is an RNA-binding and a major component of aggregates found in amyotrophic lateral sclerosis several other neurodegenerative diseases. TDP-43 exists as full-length two shorter forms 25 35 kDa. Full-length mutant TDP-43s patients re-localize from the nucleus to cytoplasm part mitochondria, where they exert toxic role associated with neurodegeneration. However, induction mitochondrial damage by fragments yet be clarified. In this work, we show that kDa...
Abstract Genetic and experimental findings point to a crucial role of RNA dysfunction in the pathogenesis Amyotrophic Lateral Sclerosis (ALS). Evidence suggests that mutations binding proteins (RBPs) such as FUS, gene associated with ALS, affect regulation alternative splicing. We have previously shown overexpression wild-type FUS mice, condition induces ALS-like phenotypes, impacts splicing hnRNP A2/B1, protein key roles metabolism, suggesting pathological connection between A2/B1 might...