A5005693249- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Computational Drug Discovery Methods
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Neurogenesis and neuroplasticity mechanisms
- Neurological Disorders and Treatments
- Memory and Neural Mechanisms
- Epilepsy research and treatment
- Neurotransmitter Receptor Influence on Behavior
- Genetics and Neurodevelopmental Disorders
- Functional Brain Connectivity Studies
- Amino Acid Enzymes and Metabolism
- Neuroendocrine regulation and behavior
- Cellular transport and secretion
- Health, Environment, Cognitive Aging
- Amyotrophic Lateral Sclerosis Research
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
University of Milan
2016-2025
University of Wisconsin–Madison
2023
Queen's University Belfast
2022
Alexandru Ioan Cuza University
2022
European Council
2011-2021
University of Milano-Bicocca
2020
Ospedali Riuniti Marche Nord
2017
Universidade Federal de São Carlos
2014
European Society of Radiology
2013
German Center for Neurodegenerative Diseases
2010
Interleukin (IL)-1β is a proinflammatory cytokine implicated in various pathophysiological conditions of the CNS involving NMDA receptor activation. Circumstantial evidence suggests that IL-1β and receptors can functionally interact. Using primary cultures rat hippocampal neurons, we investigated whether affects function(s) by studying (1) receptor-induced [Ca 2+ ] i increase (2) NMDA-mediated neurotoxicity. IL1β (0.01-0.1 ng/ml) dose-dependently enhances NMDA-induced increases with maximal...
PCSK9 promotes the degradation of low-density lipoprotein receptors and its inhibition by monoclonal antibodies or gene silencing approaches results in reduction plasma cholesterol levels coupled to that cardiovascular events. Notably, while liver is primary source circulating PCSK9, this protein also abundantly expressed brain. However, specific functions brain remain poorly understood. Here, we demonstrate neuron-specific knockout mice exhibit impaired cognitive function, driven...
Autoantibodies targeting the GluA3 subunit of AMPA receptors (AMPARs) are implicated in various neurological disorders, including Rasmussen's encephalitis, epilepsy, and frontotemporal dementia. However, their precise role disease pathology remains insufficiently understood. This study investigated long-term effects human anti-GluA3 antibodies (anti-GluA3 hIgGs) on neuronal morphology function using primary rat hippocampal neurons. We found that exposure to hIgGs leads delocalisation...
Abnormal function of NMDA receptor has been suggested to be correlated with the pathogenesis Parkinson’s disease (PD) as well development l -3,4-dihydroxyphenylalanine ( -DOPA)-induced dyskinesia. Here we show that NR2 subunits display specific alterations their subcellular distribution in striata from unilateral 6-hydroxydopamine-lesioned, -DOPA-treated dyskinetic, and nondyskinetic rats. Dyskinetic animals have significantly higher levels NR2A subunit postsynaptic compartment than all...
It has been recently demonstrated that the 43-kDa transactive response (TAR)-DNA-binding protein (TARDBP) is neuropathological hallmark of Frontotemporal Dementia (FTD) with ubiquitin-positive and tau-negative inclusions. Large series FTD patients without motor neuron disease have previously analysed, but no TARDBP mutation was identified. The aim present study to evaluate whether gene mutations may be associated FTD. We report a pathogenetic causative behavioural variant (bvFTD). An aged...
Appearance of dyskinesia is a common problem long-term l-DOPA treatment in Parkinson's disease patients and represents major limitation for the pharmacological management motor symptoms advanced stages. We have recently demonstrated that dopamine released from serotonin neurons responsible l-DOPA-induced 6-hydroxydopamine (6-OHDA)-lesioned rats, raising possibility blockade neuron activity by combination 5-HT1A 5-HT1B agonists could reduce dyskinesia. In present study, we investigated...
Members of membrane-bound disintegrin metalloproteinases (ADAMs) were shown to be capable cleaving amyloid precursor protein (APP) at the α-cleavage site in different cell systems. One candidate α-secretases identified this family is ADAM10. The present study addresses following major questions: 1) Are levels an α-secretase (i.e., ADAM10) reduced accessible cells Alzheimer Disease (AD) patients? 2) ADAM10 peripheral AD patients related a concomitant decrease αAPPs? Western Blot analysis...
Activation of dopamine D1 receptors is critical for the generation glutamate-induced long-term potentiation at corticostriatal synapses. In this study, we report that, in striatal neurons, are co-localized with N-methyl-d-aspartate (NMDA) postsynaptic density and that they co-immunoprecipitate NMDA receptor subunits from preparations. Using modified bioluminescence resonance energy transfer, demonstrate clustering reflects existence direct interactions. The tagged NR1 subunit cotransfected...
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 correct interplay between dopamine (DA) and glutamate is essential for corticostriatal synaptic plasticity motor activity. In an experimental model of Parkinson's disease (PD) obtained in rats, the complete depletion striatal DA, mimicking advanced stages disease, results loss both forms plasticity: long-term potentiation (LTP) depression (LTD). However, early PD are characterized by incomplete reduction DA levels. The mechanism which this level affects glutamatergic synapses unknown. Here...
Abstract Clin Chem Lab Med 2006;44:1472–80.
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...
The discovery of the molecular mechanisms regulating abundance synaptic NMDA receptors is essential for understanding how plasticity, as well excitotoxic events, are regulated. However, a complete precise composition receptor complex at hippocampal synapse still missing. Here, we show that 2 h CaMKII inhibition leads to specific reduction NR2B-containing without affecting localization NR2A subunit; this event accompanied by dramatic in induction long-term potentiation (LTP), while depression...
Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of disease, synaptic mechanisms underlying impairment this pathology are unknown.Hippocampal long-term potentiation represents major experimental model for changes learning and memory is controlled by endogenous dopamine.We found that hippocampal altered both a neurotoxic transgenic plastic alteration associated an impaired dopaminergic transmission decrease NR2A/NR2B subunit ratio...
Abstract Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that contributes to neuronal injury in various degenerative diseases, and therefore potential therapeutic target. It exerts its biological effect by activating the interleukin-1 receptor type I (IL-1RI) recruiting signalling core complex consisting of myeloid differentiation primary response protein 88 (MyD88) IL-1R accessory (IL-1RAcP). This pathway has been clearly described peripheral immune system, but only scattered...
A disintegrin and metalloproteinase 10 (ADAM10), a that resides in the postsynaptic densities (PSDs) of excitatory synapses, has previously been shown to limit β-amyloid peptide (Aβ) formation Alzheimer's disease (AD). ADAM10 also plays critical role regulating functional membrane proteins at synapse. Using human hippocampal homogenates, we found removal from plasma was mediated by clathrin-dependent endocytosis. Additionally, identified clathrin adaptor AP2 as an interacting partner...
Abstract: NMDA receptors and Ca 2+ /calmodulin‐dependent kinase II (CaMKII) have been reported to be highly concentrated in the postsynaptic density (PSD). Although possibility that CaMKII PSD might associated with specific proteins has put forward, protein or determining targeting of not yet identified. Here we report binds NR2A NR2B subunits isolated from cortex hippocampus. The association receptor was assessed by immunoprecipitating antibodies for NR2A/B CaMKII: coprecipitated NR1 but...
Amyloid precursor protein (APP), ADAM 10, and β-site-APP cleaving enzyme (BACE) alterations were evaluated in platelets of 31 patients with Alzheimer disease (AD) 15 age-matched controls. A significant modification these proteins enzymes involved the amyloid cascade was detected from earliest clinically detectable stage. This observation suggests that AD is associated an early metabolic derangement toward amyloidogenic pathways supports potential value APP secretase measurements for diagnosis AD.