A5039694674- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- Nerve injury and regeneration
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Nicotinic Acetylcholine Receptors Study
- Medicinal Plants and Neuroprotection
- Cholinesterase and Neurodegenerative Diseases
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Neuroscience and Neural Engineering
- Signaling Pathways in Disease
- Nuclear Receptors and Signaling
- Family and Disability Support Research
- Genomics and Chromatin Dynamics
- Neurotransmitter Receptor Influence on Behavior
Vita-Salute San Raffaele University
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2021-2024
San Raffaele University of Rome
2010-2018
Mario Negri Institute for Pharmacological Research
2015-2016
Neuroscience Institute
2010-2015
University of Milan
2008
l -dopa–induced dyskinesia (LID) is a common debilitating complication of dopamine replacement therapy in Parkinson's disease. Recent evidence suggests that LID may be linked causally to hyperactivation the Ras–ERK signaling cascade basal ganglia. We set out determine whether specific targeting Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), brain-specific activator pathway, provide for LID. On rodent abnormal involuntary movements scale, Ras-GRF1–deficient mice were significantly...
The lack of technology for direct global-scale targeting the adult mouse nervous system has hindered research on brain processing and dysfunctions. Currently, gene transfer is normally achieved by intraparenchymal viral injections, but these injections target a restricted area. Herein, we demonstrated that intravenous delivery adeno-associated virus (AAV)-PHP.B particles permeated diffused throughout neural parenchyma, both central peripheral in global pattern. We then established multiple...
Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy this disease presents inherent hurdles since MECP2 expressed throughout brain and its duplication leads to severe neurological conditions as well. Herein, we use AAV-PHP.eB deliver instability-prone Mecp2 (iMecp2) transgene cassette which, increasing RNA destabilization inefficient protein translation of viral transgene, limits...
Ras-ERK signalling in the brain plays a central role drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested experimental models addiction, necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 that penetrate and, micromolar range, inhibit phosphorylation ERK, histone H3 S6 ribosomal protein striatal slices. Furthermore, screening small therapeutics currently trials for cancer therapy revealed PD325901 as...
Abstract Cell signaling is central to neuronal activity and its dysregulation may lead neurodegeneration cognitive decline. Here, we show that selective genetic potentiation of ERK prevents cell death in vitro vivo the mouse brain, while attenuation does opposite. This neuroprotective effect mediated by an enhanced nuclear can also be induced novel penetrating peptide RB5. In administration RB5 disrupts preferential interaction ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates...
The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they generally mediated by the secretion immunomodulatory neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents first cause severe intellectual disability girls, might benefit from NPC-based therapy. Using vitro co-cultures, we demonstrate that, sensing pathological context, NPC-secreted factors induce recovery morphological...
Recent findings have shown that pharmacogenetic manipulations of the Ras-ERK pathway provide a therapeutic means to tackle l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID). First, we investigated whether prolonged l-DOPA treatment differentially affected ERK signaling in medium spiny neurons direct (dMSNs) and cholinergic aspiny interneurons (ChIs) assessed role Ras-GRF1 both subpopulations. Second, using viral-assisted technology, probed Ras-GRF2 as potential targets this...
TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein involved in the modulation of important cellular pathways and master regulators transcriptional output, including nuclear receptor repressors, Wnt signaling, MECP2 protein. However, mutations (including complete loss its functions) have not been experimentally studied a context, leaving knowledge gap mechanisms at basis diseases. Here, we show that Tbl1xr1 knock-out...
Abstract MECP2 deficiency causes a broad spectrum of neuropsychiatric disorders that can affect both genders. Rett syndrome is the most common and characterized by an apparently normal growth period followed regression phase in which patients lose their previously acquired skills. After this dramatic period, various symptoms progressively appear, including severe intellectual disability, epilepsy, apraxia, breathing abnormalities motor deterioration. encodes for epigenetic transcription...
The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they generally mediated by the secretion immunomodulatory neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents first cause severe intellectual disability girls, might benefit from an NPC-based therapy. Using vitro co-cultures, we demonstrate that, sensing pathological context, NPC-secreted factors induce recovery...
Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead neurodegenerative processes associated cognitive decline. So far, a major effort has been directed toward the dissection of disease specific pathways with still unmet promise develop precision medicine strategies. With different approach, here we show that selective genetic potentiation ERK prevents cell death in vitro vivo mouse brain while attenuation does opposite. This neuroprotective effect can...
Abstract Rett syndrome (RTT) is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy this disease presents inherent hurdles since MECP2 expressed throughout brain and its duplication leads to severe neurological conditions as well. However, recent introduction of AAV-PHP.eB, engineered capsid with unprecedented efficiency crossing blood-brain barrier upon intravenous injection, has provided invaluable vehicle...