A5028381163- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Photoreceptor and optogenetics research
- Sleep and Wakefulness Research
- Migraine and Headache Studies
- Trigeminal Neuralgia and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Toxin Mechanisms and Immunotoxins
- Heat shock proteins research
- Neurological Complications and Syndromes
- Anesthesia and Neurotoxicity Research
- Autophagy in Disease and Therapy
- Genomics and Chromatin Dynamics
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Sleep and related disorders
- CRISPR and Genetic Engineering
- Neonatal and fetal brain pathology
- Intracranial Aneurysms: Treatment and Complications
- Advanced Fluorescence Microscopy Techniques
IRCCS Humanitas Research Hospital
2023-2025
University College London
2019-2024
National Hospital for Neurology and Neurosurgery
2019-2024
Humanitas University
2022-2024
Italian Institute of Technology
2014-2016
University of Genoa
2012-2016
Triggering receptor expressed on myeloid cells 2 (Trem2) is a cell-specific gene in brain microglia, with variants that are associated neurodegenerative diseases, including Alzheimer's disease. Trem2 essential for microglia-mediated synaptic refinement, but whether contributes to shaping neuronal development remains unclear. Here, we demonstrate plays key role controlling the bioenergetic profile of pyramidal neurons during development. In absence Trem2, developing hippocampal cornus ammonis...
Cyclin-dependent kinase-5 (Cdk5) was reported to downscale neurotransmission by sequestering synaptic vesicles (SVs) in the release-reluctant resting pool, but molecular targets mediating this activity remain unknown. Synapsin I (SynI), a major SV phosphoprotein involved regulation of trafficking and neurotransmitter release, is one presynaptic substrates Cdk5, which phosphorylates it its C-terminal region at Ser 549 (site 6) 551 7). Here we demonstrate that Cdk5 phosphorylation SynI fine...
Significance Release of neurotransmitters relies on submillisecond coupling synaptic vesicle fusion to the triggering signal: AP-evoked presynaptic Ca 2+ influx. The key player that controls exocytosis is sensor synaptotagmin 1 (Syt1). While activation Syt1 has been extensively characterized, how reversibly clamps vesicular remains enigmatic. Here, using a targeted mutation combined with fluorescence imaging and electrophysiology, we show structural feature self-oligomerize provides...
Abstract The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties neuronal synapses regulation network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular tens to hundreds individual synaptic outputs from pyramidal cells with 4 millisecond temporal 75 nm spatial resolution. We find that...
DNAJC6 encodes auxilin, a co-chaperone protein involved in clathrin-mediated endocytosis (CME) at the presynaptic terminal. Biallelic mutations cause complex, early-onset neurodegenerative disorder characterized by rapidly progressive parkinsonism-dystonia childhood. The disease is commonly associated with additional neurodevelopmental, neurological and neuropsychiatric features. Currently, there are no disease-modifying treatments for this condition, resulting significant morbidity risk of...
Recycling of synaptic vesicles (SVs) is a fundamental step in the process neurotransmission. Endocytosed SV can travel directly into recycling pool or recycle through endosomes but little known about molecular actors regulating switch between these routes. ADP ribosylation factor 6 (Arf6) small GTPase to participate constitutive trafficking plasma membrane and early endosomes. Here, we have morphologically functionally investigated Arf6-silenced hippocampal synapses found an activity...
The ErbB2 receptor is a clinically validated cancer target whose internalization and trafficking mechanisms remain poorly understood. HSP90 inhibitors, such as geldanamycin (GA), have been developed to the degradation or modulate downstream signaling. Despite intense investigations, entry route postendocytic sorting of upon GA stimulation remained controversial. We report that levels inversely impact cell clathrin-mediated endocytosis (CME) capacity. Indeed, high are responsible for its own...
A noninvasive sleep screen uncovers a Vamp2 mouse mutation with synaptic deficits underlying substantial disturbances.
Neratinib (NE) is an irreversible pan-ERBB tyrosine kinase inhibitor used to treat breast cancers (BCa) with amplification of the ERBB2/HER2/Neu gene or overexpression ERBB2 receptor. However, mechanisms behind this process are not fully understood. Here we investigated effects NE on critical cell survival processes in ERBB2+ cancer cells. By kinome array analysis, showed that time-dependently inhibited phosphorylation two distinct sets kinases. The first set, including downstream signaling...
Dissociated primary neuronal cultures are widely used as a model system to investigate the cellular and molecular properties of diverse populations mechanisms action potential generation synaptic transmission. Typically, rodent obtained from freshly-dissociated embryonic or postnatal brain tissue, which often requires intense animal husbandry. This can strain resources when working with genetically modified mice. Here we describe an experimental protocol for frozen storage mouse hippocampi,...
Breast cancers (BCa) with ERBB2 amplification show rapid tumor growth, increased disease progression, and lower survival rate. Deregulated intracellular trafficking extracellular vesicle (EVs) release are mechanisms that support cancer progression resistance to treatments. Neratinib (NE) is a Food Drug Administration–approved pan-ERBB inhibitor employed for the treatment of + BCa blocks signaling causes inhibition. However, effects NE on internalization, its multivesicular bodies (MVBs), EVs...
Abstract Synaptotagmin1 (Syt1) synchronises neurotransmitter release to action potentials acting as the fast Ca 2+ sensor and inhibitor (clamp) of spontaneous delayed asynchronous release. Whilst Syt1 activation mechanism has been well characterised, how clamps transmitter remains enigmatic. Here we show that C2B domain-dependent oligomerisation provides molecular basis for clamping function. This follows from investigation a designed mutation (F349A), which selectively destabilises...
Abstract The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties neuronal synapses regulation network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular tens to hundreds individual synaptic outputs (presynaptic boutons) from pyramidal cells culture with 4 millisecond temporal...
Approximately 20%–30% of breast cancers (BCa) harbor amplification the ERBB2/HER2/Neu gene or overexpression ERBB2 receptor. Neratinib (NE) is an irreversible pan-ERBB tyrosine kinase inhibitor that causes survival inhibition ERBB2+ cancer cells and currently approved only for BCa. Autophagy mitochondrial homeostasis are physiological processes exploited by to survive controlled TFEB TFE3 transcription factors. Whether NE affects autophagy bioenergetics suppress progression/dissemination...
Abstract Sleep-wake transitions are modulated through extensive subcortical networks although the precise roles of their individual components remain elusive. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterised by reduced propensity to transition between all sleep states while profound loss total REM time was evident. The causative mutation, an Ile102Asn substitution VAMP2, associated with substantial synaptic changes vitro...
Abstract The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties neuronal synapses regulation network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular tens to hundreds individual synaptic outputs from pyramidal cells with 4 millisecond temporal 75 nm spatial resolution. We find that...