Elena Vezzoli

• University of Milan

Synaptic dysfunction is an early pathogenic event leading to cognitive decline in Huntington’s disease (HD). We previously reported that the active ADAM10 level is increased in the HD cortex and striatum, causing excessive proteolysis of the synaptic cell adhesion protein N-Cadherin. Conversely, ADAM10 inhibition is neuroprotective and prevents cog...

Huntington’s disease (HD) causes selective degeneration of striatal and cortical neurons, resulting in cell mosaicism of coexisting still functional and dysfunctional cells. The impact of non-cell autonomous mechanisms between these cellular states is poorly understood. Here we generated telencephalic organoids with healthy or HD cells, grown separ...

Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway us...

Mammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. The in vitro generation of oRG is essential to model and investigate the underlying mechanisms of human neocortical development and expansion. By ac...

Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from stem cell-derived single neural rosettes and investigate tele...

Background A disintegrin and metalloproteinase 10 (ADAM10) is a constitutive alpha-secretase found at the excitatory synapse and implicated in the molecular structure and function of adult neuronal circuitries. Recently, we described that active ADAM10 increases at the synapse in Huntington’s Disease (HD) striatum and cortex and impairs both the pr...

Objectives Evaluate the ability of current ion-releasing materials to remineralise bacteria-driven artificial caries lesions. Materials and methods Standardised class I cavities were obtained in 60 extracted human molars. Specimens underwent a microbiological cariogenic protocol (28 days) to generate artificial caries lesions and then were randoml...

Background ADAM10 is a major protease of the human brain and regulates the strength and activity of the glutamatergic synapse by cleaving a large repertoire of synaptic substrates. In Huntington’s Disease (HD), active ADAM10 accumulates at the postsynaptic density and causes proteolysis of the cell adhesion protein Ncadherin, loss of excitatory syn...

Human mutations and haploinsufficiency of the SHANK family genes are associated with autism spectrum disorders (ASD) and intellectual disability (ID). Complex phenotypes have been also described in all mouse models of Shank mutations and deletions, consistent with the heterogeneity of the human phenotypes. However, the specific role of Shank protei...

Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia’s oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow...

Development of the human striatum revealed Deep in the brain, the striatum receives and coordinates inputs from other parts of the brain. Bocchi et al. surveyed molecular features as the striatum develops in the human brain. Single-cell surveys of long intergenic noncoding RNAs revealed a progenitor for medium spiny neurons and provide insight into...

Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia’s oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow...

Synaptic dysfunction and cognitive decline in Huntington's disease (HD) involve hyperactive A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). To identify the molecular mechanisms through which ADAM10 is associated with synaptic dysfunction in HD, we performed an immunoaffinity purification-mass spectrometry (IP-MS) study of...

Our understanding of the human brain is limited by the lack of experimental models to mechanistically probe the properties of brain cells at different developmental stages under normal and pathological conditions. We developed a new method for generating human cortico-striatal organoids from stem cell-derived single neural rosettes (SNRs) and used...

Mechanotransduction is the ability of cells to translate mechanical stimuli into biochemical signals that can ultimately influence gene expression, cell morphology and cell fate. Tenocytes are responsible for tendon mechanical adaptation converting mechanical stimuli imposed during mechanical loading, thus affecting extracellular matrix homeostasis...

Detecting the ultrastructure of brain tissue in human archaeological remains is a rare event that can offer unique insights into the structure of the ancient central nervous system (CNS). Yet ancient brains reported in the literature show only poor preservation of neuronal structures. Using scanning electron microscopy (SEM) and advanced image proc...

Purpose: To investigate whether the addition of sodium-DNA (Na-DNA) to chlorhexidine (CHX)-containing mouthwash influenced morphology and viability of a reconstituted human oral epithelium (ROE), and protects ROE against oxidative stress. Methods: Multi-layered 0.5 cm² ROE specimens were positioned inside a continuous flow bioreactor and grown a...

A variety of pathophysiological mechanisms are implicated in Huntington's disease (HD). Among them, reduced cholesterol biosynthesis has been detected in the HD mouse brain from pre-symptomatic stages, leading to diminished cholesterol synthesis, particularly in the striatum. In addition, systemic injection of cholesterol-loaded brain-permeable nan...

Theranostics based on two-photon excitation of therapeutics in the NIR region is an emerging and powerful tool in cancer therapy since this radiation deeply penetrates healthy biological tissues and produces selective cell death. Aggregates of gold nanoparticles coated with glutathione corona functionalized with the dansyl chromophore (a-DG-AuNPs)...

A variety of pathophysiological mechanisms are implicated in Huntington's disease (HD). Among them, reduced cholesterol biosynthesis has been detected in the HD mouse brain from pre-symptomatic stages, leading to diminished cholesterol synthesis, particularly in the striatum. In addition, systemic injection of cholesterol-loaded brain-permeable nan...

Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice a...

A disintegrine and metalloproteinase 10 (ADAM10) is implicated in synaptic function through its interaction with postsynaptic receptors and adhesion molecules. Here, we report that levels of active ADAM10 are increased in Huntington's disease (HD) mouse cortices and striata and in human postmortem caudate. We show that, in the presence of polygluta...

The rapid involution that happens in some muscles of ungulate fetlock joints has never been investigated at an ultrastructural level. In this study, the proximal sesamoidean ligament (PSL) of sheep was chosen as a model to investigate, at the cellular level, the transition from muscle to connective structures that occurs during early development. I...

There are numerous studies showing a reduction in cholesterol biosynthesis in the brain of different HD animal models of HD since pre-symptomatic stages, with the striatum being more affected compared to other brain tissues (Valenza et al., 2005; 2007; 2010; Shankaran et al., 2017). Abnormalities in brain cholesterol homeostasis are also present in...

Intellectual disability affects 2–3% of the world's population and typically begins during childhood, causing impairments in social skills and cognitive abilities. Mutations in the TM4SF2 gene, which encodes the TSPAN7 protein, cause a severe form of intellectual disability, and currently, no therapy is able to ameliorate this cognitive impairment....

Aims: Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 varia...

Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulat...

Myosin IXa (Myo9a) is a motor protein that is highly expressed in the brain. However, the role of Myo9a in neurons remains unknown. Here, we investigated Myo9a function in hippocampal synapses. In rat hippocampal neurons, Myo9a localizes to the postsynaptic density (PSD) and binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid recept...

div class="title">mApoE-Functionalized Nanoliposomes Delivering Doxorubicin and Ultrasmall Superparamagnetic Iron Oxide to Glioblastoma Cells Characterized by TEM and Confocal Microscopy - Volume 21 Issue S3 - Simona Rodighiero, Maria Gregori, Maura Francolini, Elena Vezzoli, Matteo Tamborini, Massimo Masserini, Michela Matteoli, Lorena Passoni

The healthy effects of numerous bioactive natural compounds and the possibility to take advantage of their beneficial physiological functions are highly valued. Although the efficacy of a number of nutraceutical products has already been demonstrated in humans, the properties of many compounds are still unknown and, importantly, there is little inf...

A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect and q...