A5054989793- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Autism Spectrum Disorder Research
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Hippo pathway signaling and YAP/TAZ
- Memory and Neural Mechanisms
- Epigenetics and DNA Methylation
- Neuropeptides and Animal Physiology
- Retinal Development and Disorders
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Neural dynamics and brain function
- Cell Image Analysis Techniques
Neuroscience Institute
2015-2025
National Research Council
2013-2023
Universität Ulm
2023
Vanderbilt Health
2023
Vanderbilt University
2023
University of Milan
2013-2022
University of Milano-Bicocca
2020-2021
Instituto de Salud Carlos III
2018
Hospital Universitari Sant Joan de Reus
2018
Institut d'Investigació Sanitària Pere Virgili
2018
Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, Shank family postsynaptic scaffold proteins are abundant enriched density (PSD) central excitatory synapses. When expressed cultured hippocampal neurons, promotes maturation enlargement spines. Recently, Shank3 has been genetically implicated human autism, suggesting an important role for normal cognitive development. Here, we report phenotype Shank1 knock-out...
Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are the single most common cause of inherited Parkinson's disease. Little is known about its involvement pathogenesis disease mainly because lack knowledge physiological role LRRK2. To determine function LRRK2, we studied impact short hairpin RNA-mediated silencing expression cortical neurons. Paired recording indicated that affects evoked postsynaptic currents. Furthermore, induces at presynaptic site a redistribution vesicles within...
Shank proteins assemble glutamate receptors with their intracellular signaling apparatus and cytoskeleton at the postsynaptic density. Whether plays a role in spinogenesis synaptogenesis remained unclear. Here, we report that knock-down of Shank3/prolinerich synapse-associated protein-2 by RNA interference reduces spine density hippocampal neurons. Moreover, transgene expression 3 is sufficient to induce functional dendritic spines aspiny cerebellar Transfected protein recruits receptors,...
The postsynaptic density (PSD) proteins Shank and Homer cooperate to induce the maturation enlargement of dendritic spines (Sala et al., 2001). Homer1a is an activity-inducible short-splice variant that lacks dimerization capacity. Here, we show reduces size in cultured hippocampal neurons correlation with inhibition targeting synapses. Expression also decreases PSD-95 clusters, number NMDA receptor level surface AMPA receptors, implying a negative effect on growth In parallel morphological...
NMDA receptors interact directly with postsynaptic density-95 (PSD-95), a scaffold protein that organizes cytoskeletal- signaling complex at the membrane. The molecular mechanism by which PSD-95-based is trafficked to site unknown but presumably involves specific motor proteins. Here we demonstrate direct interaction between PSD-95-associated guanylate kinase domain-associated (GKAP) and dynein light chain (DLC), subunit shared myosin-V (an actin-based motor) cytoplasmic (a microtubule-based...
Shank3/PROSAP2 gene mutations are associated with cognitive impairment ranging from mental retardation to autism. Shank3 is a large scaffold postsynaptic density protein implicated in dendritic spines and synapse formation; however, its specific functions have not been clearly demonstrated. We used RNAi knockdown expression neuronal cultures showed that this treatment specifically reduced the synaptic of metabotropic glutamate receptor 5 (mGluR5), but did affect other major proteins. The...
Alzheimer's disease (AD) is a chronic neurodegenerative disorder caused by combination of events impairing normal neuronal function. Here we found molecular bridge between key elements primary and secondary pathogenic in AD, namely the amyloid cascade synaptic dysfunction associated with glutamatergic system. In fact, report that synapse-associated protein-97 (SAP97), protein involved dynamic trafficking proteins to excitatory synapse, responsible for driving ADAM10 (a disintegrin...
A variety of chromatin remodeling complexes are thought to orchestrate transcriptional programs that lead neuronal precursors from earliest commitment terminal differentiation. Here we show mammalian neurons have a specialized enzyme arising neurospecific splice variant LSD1/KDM1, histone lysine specific demethylase 1, whose activity on Lys4 H3 has been related gene repression. We found alternative splicing LSD1 transcript generates four full-length isoforms combinatorial retention two...
Activity-dependent changes in synaptic structure and spine morphology are required for learning memory, depend on protein translation. We show that the kinase eukaryotic elongation factor 2 (eEF2K) regulates dendritic stability by modulating activity-dependent BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces inhibits expression; whereas overexpression a constitutively activated induces maturation increases expression BDNF. Furthermore, rescues reduced eEF2K. also...
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including predicted C-terminal WD40 repeats. In this study, we analyzed functional molecular features conferred by domain. Electron microscopic analysis purified domain revealed doughnut-shaped particles, providing experimental evidence for its fold. We demonstrate binds sequesters synaptic vesicles via...