A5064846884- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Ion Transport and Channel Regulation
- Epilepsy research and treatment
- Signaling Pathways in Disease
- Down syndrome and intellectual disability research
- RNA Interference and Gene Delivery
- Cardiac electrophysiology and arrhythmias
- 14-3-3 protein interactions
- Ion channel regulation and function
- Neonatal Respiratory Health Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Autism Spectrum Disorder Research
- Biochemical and Structural Characterization
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- S100 Proteins and Annexins
- Infant Development and Preterm Care
- Neonatal and fetal brain pathology
- Lipid Membrane Structure and Behavior
- Analog and Mixed-Signal Circuit Design
- Neurogenesis and neuroplasticity mechanisms
Italian Institute of Technology
2017-2024
Dulbecco Telethon Institute
2021-2022
University of Genoa
2017-2020
Telethon Foundation
2020
Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to system. In hippocampus Dp(16) mouse model DS individuals, we found activated microglia, as assessed their morphology; activation markers; and, mice, electrophysiological profile. Accordingly, increased pro-inflammatory cytokine levels...
Aberrant expression ratio of Cl− transporters, NKCC1 and KCC2, is implicated in several brain conditions. inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms rodent models and/or clinical trials with patients. However, bumetanide has a strong effect due to kidney transporter NKCC2, creating critical drug compliance issues health concerns. Here, we report discovery new chemical class selective inhibitors lead candidate ARN23746. ARN23746 restores physiological...
Alterations in the expression of Cl
Intracellular chloride concentration [Cl–]i is defective in several neurological disorders. In neurons, mainly regulated by the action of Na+–K+–Cl– importer NKCC1 and K+–Cl– exporter KCC2. Recently, we have reported discovery ARN23746 as lead candidate a novel class selective inhibitors NKCC1. Importantly, able to rescue core symptoms Down syndrome (DS) autism mouse models. Here, describe extensive characterization this chemical inhibitors, with focus on other promising derivatives....
Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal hormone utero, and low IGF-1 serum levels correlate with poor neurodevelopmental outcomes. Here, we mimicked deficiency of mice by perinatal administration an receptor antagonist. This resulted brain microstructural, functional, alterations, resembling those ex-preterm children, which characterized...
Highlights•APache is a presynaptic AP2 interactor on clathrin-coated vesicles•APache silencing affects the early neuronal development in vitro and vivo•APache-silenced synapses exhibit marked endocytic phenotype•APache impairs clathrin-mediated endocytosis synaptic functionSummarySynaptic transmission critically dependent vesicle (SV) recycling. Although precise mechanisms of SV retrieval are still debated, it widely accepted that fundamental role played by endocytosis, form capitalizes...
Protocadherin 19 gene-related epilepsy or protocadherin clustering is an infantile-onset syndrome characterized by psychiatric (including autism-related), sensory, and cognitive impairment of varying degrees. caused X-linked protein loss function. Due to random X-chromosome inactivation, epilepsy-affected females present a mosaic population healthy 19-mutant cells. Unfortunately, date, no current mouse model can fully recapitulate both the brain histological behavioural deficits in people...
<h3>Objective:</h3> The aim of this work was to search for selective NKCC1 inhibitors devoid undesired diuretic effects as a sustainable therapeutic solution brain disorders characterized by defective NKCC1/KCC2 expression-ratio. <h3>Background:</h3> Proper intracellular chloride concentration is fundamental physiological development and function. Accordingly, the aberrant expression-ratio chloride-importer -exporter KCC2 implicated in several conditions, including drug-resistant epilepsy...