A5008693949- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Genomic variations and chromosomal abnormalities
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Neuroscience and Neural Engineering
- Trace Elements in Health
- Genetic and Kidney Cyst Diseases
- Nuclear Receptors and Signaling
- Biomedical Research and Pathophysiology
- Pesticide and Herbicide Environmental Studies
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Medicinal Plants and Neuroprotection
- Biotin and Related Studies
- Ion channel regulation and function
- Nerve injury and regeneration
- Synthesis of Indole Derivatives
- Renal and related cancers
- Cholinesterase and Neurodegenerative Diseases
University of Turin
2016-2024
University of Wisconsin–Madison
2023
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2020
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2015-2020
Vita-Salute San Raffaele University
2020
Dulbecco Telethon Institute
2015
Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature ADPKD, and inhibition glycolysis using analogs ameliorates aggressive PKD preclinical models. Here, we investigated effects chronic treatment with low doses analog 2-deoxy- d -glucose (2DG) on ADPKD progression orthologous slowly progressive murine models created by inducible...
RAB39B is a member of the RAB family small GTPases that controls intracellular vesicular trafficking in compartment-specific manner. Mutations gene cause intellectual disability comorbid with autism spectrum disorder and epilepsy, but impact loss function on synaptic activity largely unexplained. Here we show protein interacting C-kinase 1 (PICK1) downstream effector GTP-bound RAB39B-PICK1 from endoplasmic reticulum to Golgi and, hence, surface expression GluA2, subunit...
Cyclin-dependent kinase-like 5 (CDKL5) mutations are found in severe neurodevelopmental disorders, including the Hanefeld variant of Rett syndrome (RTT; CDKL5 disorder). loss-of-function murine models recapitulate pathological signs human disease, such as visual attention deficits and reduced acuity. Here we investigated cellular synaptic substrates defects by studying organization primary cortex (V1) Cdkl5-/y mice. We a reduction c-Fos expression V1 mutants, suggesting circuit hypoactivity....
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...
CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disease caused by mutations in the X-linked gene. Children affected CDD display clinical phenotype characterized early-onset epilepsy, intellectual disability, motor impairment, and autistic-like features. Although aspects associated with are well described children, adults still under-characterized. Similarly, most animal research has been carried out on young adult Cdkl5 knockout (KO) mice only. Since age represents risk factor...
GDI1 gene encodes for αGDI, a protein controlling the cycling of small GTPases, reputed to orchestrate vesicle trafficking. Mutations in human are responsible intellectual disability (ID). In mice with ablated Gdi1, model ID, impaired working and associative short-term memory was recorded. This cognitive phenotype worsens if deletion αGDI expression is restricted neurons. However, whether astrocytes, key homeostasis providing neuroglial cells, supporting neurons via aerobic glycolysis,...
RPH3A encodes a protein involved in the stabilization of GluN2A subunit N-methyl-D-aspartate (NMDA)-type glutamate receptors at cell surface, forming complex essential for synaptic plasticity and cognition. We investigated effect variants patients with neurodevelopmental disorders.By using trio-based exome sequencing, GeneMatcher, screening 100,000 Genomes Project data, we identified 6 heterozygous RPH3A. In silico vitro models, including rat hippocampal neuronal cultures, have been used to...
ABSTRACT Mutations of the cyclin-dependent kinase-like 5 (CDKL5) gene, which encodes a serine/threonine protein kinase, can cause CDKL5 deficiency disorder (CDD), severe neurodevelopmental disease characterized by epileptic encephalopathy and neurocognitive impairment. The kinase consists catalytic N-terminal domain (NTD) less C-terminal (CTD). Numerous disease-related mutations truncate CDKL5, leaving NTD intact while variably shortening CTD, highlights importance CTD for function. By...
Autistic traits may arise from atypical sensory experience during postnatal life, but whether there is a causal link between defects in cortical circuitry the brain, altered processing and social behavior remains unknown. Here, we studied tactile stimuli barrel cortex (BC) interactions juvenile male mice lacking Cyclin-dependent kinase-like 5 (CDKL5), model of severe neurodevelopmental disease showing autistic impairments. We identified these whisker-dependent sensorimotor reflexes, NMDA...
Mammalian target of rapamycin (mTOR) pathway has emerged as a key molecular mechanism underlying memory processes. Although mTOR inhibition is known to block processes, it remains elusive whether and how an enhancement signaling may improve Here we found in male mice that the administration VO-OHpic, inhibitor phosphatase tensin homolog (PTEN) negatively modulates AKT-mTOR pathway, enhanced auditory fear for days weeks, while left short-term unchanged. Memory was associated with long-lasting...
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 Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a devastating rare neurodevelopmental disease without cure, caused by mutations of the serine/threonine kinase CDKL5 highly expressed in forebrain. CDD characterized early-onset seizures, severe intellectual disabilities, autistic-like traits, sensorimotor and cortical visual impairments (CVI). The lack an effective therapeutic strategy for urgently demands identification novel druggable targets potentially relevant...