Silvia Sacchi

ORCID: 0000-0002-2338-2561
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About
Contact & Profiles
Research Areas
  • Amino Acid Enzymes and Metabolism
  • Epigenetics and DNA Methylation
  • Metabolism and Genetic Disorders
  • Tryptophan and brain disorders
  • Neuroscience and Neuropharmacology Research
  • Polyamine Metabolism and Applications
  • Diet and metabolism studies
  • Enzyme Structure and Function
  • Receptor Mechanisms and Signaling
  • Laser Applications in Dentistry and Medicine
  • Cancer, Hypoxia, and Metabolism
  • Chemical Synthesis and Analysis
  • Cancer Research and Treatments
  • Photoreceptor and optogenetics research
  • Alzheimer's disease research and treatments
  • Chronic Lymphocytic Leukemia Research
  • Enzyme Catalysis and Immobilization
  • Enzyme function and inhibition
  • Photosynthetic Processes and Mechanisms
  • Aquatic Ecosystems and Phytoplankton Dynamics
  • Skin Protection and Aging
  • Mitochondrial Function and Pathology
  • Medical and Biological Ozone Research
  • Marine Toxins and Detection Methods
  • Cholinesterase and Neurodegenerative Diseases

University of Insubria
2016-2025

Politecnico di Milano
2010-2018

Institute of Chemistry of Molecular Recognition
2014

University of Gothenburg
2013

Regione Lombardia
2011

University of Milan
1998-1999

Istituto di Chimica Biomolecolare
1997-1998

University of Oslo
1998

Istituti di Ricovero e Cura a Carattere Scientifico
1989

N-methyl-D-aspartate receptors (NMDARs) subserve numerous neurophysiological and neuropathological processes in the cerebral cortex. Their activation requires binding of glutamate also a coagonist. Whereas glycine D-serine (D-ser) are candidates for such role at central synapses, nature coagonist cortex remains unknown. We first show that glycine-binding site NMDARs is not saturated acute slices preparations medial prefrontal (mPFC). Using enzymes selectively degrade either D-ser or glycine,...

10.1093/cercor/bhr130 article EN Cerebral Cortex 2011-06-20

Human genes coding for pLG72 and d-amino acid oxidase have recently been linked to the onset of schizophrenia. was proposed as an activator human FAD-containing flavoprotein (hDAAO). In brain this oxidizes d-serine, a potent N-methyl-d-aspartate receptor. We investigated mechanistic regulation hDAAO by pLG72. Immunohistochemical analyses revealed that are both expressed in astrocytes cortex, where they most likely interact, considering their partial overlapping subcellular distribution...

10.1074/jbc.m709153200 article EN cc-by Journal of Biological Chemistry 2008-06-11

Significance NMDA receptors (NMDARs) support patterning and activity of synapses throughout life are central to many brain disorders. The NMDAR activation requires the concomitant binding glutamate a coagonist glycine or d -serine. To date, whether preference for one at specific connections occurs remains unsolved. Here, we sought determine when where -serine enter into play hippocampal synapses. We demonstrate that identity is synapse developmentally regulated. Remarkably, this segregation...

10.1073/pnas.1416668112 article EN Proceedings of the National Academy of Sciences 2014-12-30

The subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content GluN2A- and GluN2B-containing receptors, greatly influences glutamate transmission. Receptor co-agonists, glycine D-serine, have intriguingly emerged potential regulators receptor trafficking in addition to their requirement for its activation. Using a combination single-molecule imaging, biochemistry electrophysiology, we show that D-serine availability at rat hippocampal glutamatergic synapses regulate...

10.7554/elife.25492 article EN cc-by eLife 2017-06-05

d ‐Amino acid oxidase (DAAO) has been proposed to be involved in the oxidation of ‐serine, an allosteric activator NMDA‐type glutamate receptor brain, and associated with onset schizophrenia. The recombinant human DAAO was expressed Escherichia coli isolated as active homodimeric flavoenzyme. It shows properties dehydrogenase‐oxidase class flavoproteins, possesses a low kinetic efficiency, follows ternary complex (sequential) mechanism. In contrast other known DAAOs, enzyme is stable...

10.1016/j.febslet.2006.03.045 article EN FEBS Letters 2006-03-24

Cocaine seeking behaviour and relapse have been linked to impaired potentiation depression at excitatory synapses in the nucleus accumbens, but mechanism underlying this process is poorly understood. We show that, rat accumbens core, d-serine endogenous coagonist of N-methyl-d-aspartate receptors, its presence essential for receptor-dependent synaptic transmission. Nucleus core slices obtained from cocaine-treated rats after 1 day abstinence presented significantly reduced concentrations,...

10.1093/brain/awt036 article EN Brain 2013-03-20

The endogenous NMDA receptor (NMDAR) agonist d -aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing adulthood. It well established that postnatal reduction of cerebral levels due to concomitant onset oxidase (DDO) activity, a flavoenzyme selectively degrades bicarboxylic -amino acids. In present work, we show content mouse decreases after birth, whereas Ddo mRNA concomitantly increase. Interestingly,...

10.1523/jneurosci.3881-15.2016 article EN cc-by-nc-sa Journal of Neuroscience 2016-03-09

It is long acknowledged that the N-methyl d-aspartate receptor co-agonist, d-serine, plays a crucial role in several receptor-mediated physiological and pathological processes, including schizophrenia. Besides another free d-amino acid, d-aspartate, involved activation of receptors acting as an agonist this subclass, abundantly detected developing human brain. Based on hypothesis hypofunction pathophysiology schizophrenia considering ability d-serine to stimulate receptor-dependent...

10.1038/s41537-017-0015-7 article EN cc-by Schizophrenia 2017-03-27

D-Serine acts as a co-agonist of N-methyl-D-aspartate receptors (NMDAR) which appear overactivated in AD, while D-aspartate is modulatory molecule acting on NMDAR second agonist. The aim this work to clarify whether the levels these D-amino acids serum are deregulated with final goal identify novel and precocious biomarkers AD. Serum L- D-enantiomers serine aspartate were determined by HPLC using pre-column derivatization procedure selective enzymatic degradation. Experimental data obtained...

10.1038/s41398-021-01202-3 article EN cc-by Translational Psychiatry 2021-01-26

Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using integrated omics approach, we investigate alterations in the molecular composition postmortem hippocampus samples healthy persons and individuals with AD. Profound differences are apparent between control AD male female cohorts terms up- downregulated metabolic pathways. A decrease insulin response evident when comparing group. The...

10.1016/j.celrep.2022.111271 article EN cc-by-nc-nd Cell Reports 2022-09-01

A filamentous cyanobacterium, belonging to the Order of Oscillatoriales, was found be responsible for a toxic algal bloom in Lake Varese, Italy, during summer 1997. Morphological characters, as well near complete 16S rRNA gene sequencing, revealed that dominant species most closely related genus Planktothrix. In addition, genetic analysis phycocyanin operon Planktothrix sp. FP1 novel primary structure, previously undescribed within cyanobacteria, which used marker rapid detection and...

10.1046/j.1529-8817.2000.99181.x article EN Journal of Phycology 2000-06-01

The effects of laser irradiations have been estimated both from the clinical point view (rate reduction ulcerated area) and in ultrastructural terms. modification produced by human fibroblasts culture also investigated. Under our experimental conditions, stimulates secretion fibroblasts, vivo vitro, for reasons that are still object research. After irradiation formation periodic collagen fibrils is not observed, so complete ‘restitutio ad integrum’ dermal matrix does occur.

10.1159/000249691 article EN Dermatology 1984-01-01

The high resolution crystal structure of D-amino-acid oxidase (DAAO) from the yeast Rhodotorula gracilis provided us with tool to engineer substrate specificity this flavo-oxidase. DAAO catalyzes oxidative deamination D-amino acids, exception D-aspartate and D-glutamate (which are oxidized by oxidase, DASPO). Following sequence homology, molecular modeling, simulated annealing docking analyses, active site residue Met-213 was mutated arginine. mutant enzyme showed properties close those...

10.1074/jbc.m203946200 article EN cc-by Journal of Biological Chemistry 2002-07-01

Abstract Lacking an efficient process to produce 7‐aminocephalosporanic acid from cephalosporin C in a single step, d ‐amino oxidase (DAAO) is of foremost importance the industrial, two‐step used for this purpose. We report detailed study on catalytic properties three available DAAOs, namely, mammalian DAAO and two others yeast ( Rhodotorula gracilis Trigonopsis variabilis ). In comparing kinetic parameters determined with both ‐alanine as substrate, efficiency enzymes microorganism at least...

10.1021/bp034206q article EN Biotechnology Progress 2004-01-01
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