A5008201501- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Caveolin-1 and cellular processes
- Protein Kinase Regulation and GTPase Signaling
- Growth Hormone and Insulin-like Growth Factors
- Neuroendocrine regulation and behavior
- Sirtuins and Resveratrol in Medicine
- Ion channel regulation and function
- Regulation of Appetite and Obesity
- Pain Mechanisms and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Ion Transport and Channel Regulation
- Computational Drug Discovery Methods
- Hypothalamic control of reproductive hormones
- Metabolism, Diabetes, and Cancer
- Pituitary Gland Disorders and Treatments
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Hormonal Regulation and Hypertension
- Melanoma and MAPK Pathways
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Epigenetics and DNA Methylation
Institute of Organic Synthesis and Photoreactivity
2016-2025
National Research Council
2016-2025
University College London
2024
University of Bologna
1981-2024
The Royal Free Hospital
2024
University of Milan
1990-2023
Innova (Italy)
2019-2023
University of Milano-Bicocca
2010-2021
Neuroscience Institute
2017
University of Genoa
2012-2015
SIRT6 is an NAD(+)-dependent deacetylase with a role in the transcriptional control of metabolism and aging but also genome stability inflammation. Broad therapeutic applications are foreseen for inhibitors, including uses diabetes, immune-mediated disorders, cancer. Here we report on identification first selective inhibitors by silico screening. The most promising leads show micromolar IC50s, have significant selectivity versus SIRT1 SIRT2, active cells, as shown increased acetylation at...
Caveolae are cholesterol/sphingolipid-rich microdomains of the plasma membrane that have been implicated in signal transduction and vesicular trafficking. Caveolins a family caveolae-associated integral proteins. Caveolin-1 -2 show widest range expression, whereas caveolin-3 expression is restricted to muscle cell types. It has previously reported little or no caveolin mRNA species detectable brain by Northern blot analyses neuroblastoma lines. However, it remains unknown whether caveolins...
We have examined the post-translational processing of G alpha subunits expressed endogenously in rat PC12 and NG108-15 rat/mouse hybrid cells, after transfection cDNA expression constructs into COS cells. Thioester-linked palmitoylation o, s, q/alpha 11 12 has been detected by metabolic labelling with [3H]palmitate immunoprecipitation. Palmitoylation o occurs post-translationally cells treated protein-synthesis inhibitors, suggesting possible dynamic acylation. C-terminal CAAX motif...
In human myometrial cells, the promiscuous coupling of oxytocin receptors (OTRs) to G(q) and G(i) leads contraction. However, activation OTRs coupled different G protein pathways can also trigger opposite cellular responses, e.g. OTR inhibits, whereas its stimulates, cell proliferation. Drug analogues capable promoting a selective receptor-G may be great pharmacological clinical importance because they target only one specific signal transduction pathway. Here, we report that atosiban, an...
Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, perturbed signaling has been linked to the pathogenesis several psychiatric disorders. However, it is still largely unknown how exactly regulates neuronal function. We show early, transient exposure vitro inhibits development hippocampal glutamatergic neurons, leading reduced dendrite complexity, synapse density, excitatory transmission, while sparing GABAergic...
Sirtuin 6 (SIRT6) is a sirtuin family member involved in wide range of physiologic and disease processes, including cancer glucose homeostasis. Based on the roles played by SIRT6 different organs, its ability to repress expression transporters glycolytic enzymes, inhibiting has been proposed as an approach for treating type 2 diabetes mellitus (T2DM). However, so far, lack small-molecule Sirt6 inhibitors hampered conduct vivo studies assess viability this strategy. We took advantage recently...
Evidence has accumulated indicating that LHRH might behave as an autocrine/paracrine growth inhibitory factor in some peripheral tumors. However, receptors tumor cells have not been fully characterized, so far. The present experiments were performed to analyze: 1) the messenger RNA expression; 2) molecular size; and 3) signal transduction pathway of prostate cancer. For these studies, human androgen-dependent LNCaP androgen-independent DU 145 cancer cell lines used. By RT-PCR, a...
Background:The cytochrome P450 (CYP) epoxygenase pathway produces arachidonic acid metabolites that are vasoactive, affect renal sodium handling, and have been proposed to play a mechanistic role in hypertension. Multiple single nucleotide polymorphisms (SNP) CYP2C8, 2C9, 2J2 soluble epoxide hydrolase (sEH) identified, many of which altered functional activity vitro. We performed case-control study determine the prevalence epoxygenase-related SNP African American individuals evaluate whether...
Oxytocin receptor is a seven transmembrane widely expressed in the CNS that triggers G(i) or G(q) protein-mediated signaling cascades leading to regulation of variety neuroendocrine and cognitive functions. We decided investigate whether how promiscuous receptor/G protein coupling affects neuronal excitability. As an experimental model, we used immortalized gonadotropin-releasing hormone-positive GN11 cell line displaying features immature, migrating olfactory neurons. Using RT-PCR analysis,...
1 Intracerebroventricular administration of diazepam or midazolam decreased the antinociceptive effect morphine in rats as measured by "tail flick" method. 2 Midazolam, injected into periaqueductal grey matter (PAG) antagonized analgesic morphine. The action was partially reversed bicuculline. 3 These findings support view that benzodiazephines on antinociception may be mediated through gamma-aminobutyric acid receptors.
Prostate cancer (PC) is the fifth leading cause of death in men, and androgen receptor (AR) represents primary target for PC treatment, even though disease frequently progresses toward androgen-independent forms. Most commercially available nonsteroidal antiandrogens show a common scaffold consisting two aromatic rings connected by linear or cyclic spacer. By taking advantage facile, one-pot click chemistry reaction, we report herein preparation small library novel 1,4-substituted triazoles...
Here we investigate the molecular mechanisms that govern targeting of G-protein α subunits to plasma membrane. For this purpose, used G<sub>i1α</sub> as a model dually acylated G-protein. We fused full-length or its extreme NH<sub>2</sub>-terminal domain (residues 1–32 1–122) green fluorescent protein (GFP) and analyzed subcellular localization these fusion proteins. show first 32 amino acids are sufficient target GFP caveolin-enriched domains membrane <i>in vivo</i>, demonstrated by...
Plasmodium falciparum dihydrofolate reductase (PfDHFR) is an important target for antimalarial chemotherapy. Unfortunately, the emergence of resistant parasites has significantly reduced efficiency classical antifolate drugs such as cycloguanil and pyrimethamine. In this study, approach toward molecular docking structures contained in Available Chemicals Directory (ACD) database to search novel inhibitors PfDHFR described. Instead whole ACD database, specific 3D pharmacophores were used...