The Experts below are selected from a list of 471 Experts worldwide ranked by ideXlab platform

Tiziano Bandiera - One of the best experts on this subject based on the ideXlab platform.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    Nature Neuroscience, 2012
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau, Tiziano Bandiera
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, that prevented anandamide internalization in vitro , interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB_1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs. After its release, the endocannabinoid anandamide is taken up from the synaptic cleft by internalization by neurons and astrocytes. Although several lines of evidence suggest that the anandamide uptake itself is a carrier-mediated diffusion process, the molecular identity of the transporter was unknown until now. Here Fu et al . show that anandamide uptake is mediated by a novel protein named FAAH-like anandamide transporter (FLAT) that is generated as an alternative splicing product of the fatty acid amide hydrolase-1 ( Faah ) mRNA.

Giovanni Bottegoni - One of the best experts on this subject based on the ideXlab platform.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    Nature Neuroscience, 2012
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau, Tiziano Bandiera
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, that prevented anandamide internalization in vitro , interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB_1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs. After its release, the endocannabinoid anandamide is taken up from the synaptic cleft by internalization by neurons and astrocytes. Although several lines of evidence suggest that the anandamide uptake itself is a carrier-mediated diffusion process, the molecular identity of the transporter was unknown until now. Here Fu et al . show that anandamide uptake is mediated by a novel protein named FAAH-like anandamide transporter (FLAT) that is generated as an alternative splicing product of the fatty acid amide hydrolase-1 ( Faah ) mRNA.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    2011
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, which remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme, fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), which lacks amidase activity but binds anandamide with low micromolar affinity and facilitates its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, block these effects. Additionally, we identify a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, which prevents anandamide internalization in vitro, interrupts anandamide deactivation in vivo, and exerts profound analgesic effects in rodent models of nociceptive and inflammatory pain, which are mediated by CB1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs

Duckett, Simon B. - One of the best experts on this subject based on the ideXlab platform.

  • A simple and cost-efficient technique to generate hyperpolarized long-lived 15N-15N nuclear spin order in a diazine by signal amplification by reversible exchange
    American Institute of Physics Inc., 2020
    Co-Authors: Roy S. S., Rayner P J, Burns M J, Duckett, Simon B.
    Abstract:

    Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique that is capable of boosting nuclear magnetic resonance sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen, as hydride ligands, and a substrate of interest to a metal catalyst to allow for polarization transfer from para-hydrogen into substrate nuclear spins. While the resulting nuclear spin populations can be dramatically larger than those normally created, their lifetime sets a strict upper limit on the experimental timeframe. Consequently, short nuclear spin lifetimes are a challenge for hyperpolarized metabolic imaging. In this report, we demonstrate how both hyperpolarization and long nuclear spin lifetime can be simultaneously achieved in nitrogen-15 containing Derivatives of pyridazine and Phthalazine by SABRE. These substrates were chosen to reflect two distinct classes of 15N2-coupled species that differ according to their chemical symmetry and thereby achieve different nuclear spin lifetimes. The pyridazine Derivative proves to exhibit a signal lifetime of �2.5 min and can be produced with a signal enhancement of �2700. In contrast, while the Phthalazine Derivative yields a superior 15 000-fold 15N signal enhancement at 11.7 T, it has a much shorter signal lifetime

  • A Simple and Cost-efficient Technique to Generate Hyperpolarized Long-lived 15N-15N Nuclear Spin Order in a Diazine by Signal Amplification by Reversible Exchange
    2020
    Co-Authors: Roy S. S., Rayner, Peter John, Burns Michael, Duckett, Simon B.
    Abstract:

    Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique and is capable of boosting Nuclear Magnetic Resonance (NMR) sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen as hydride ligands and a substrate of interest to a metal catalyst to allow polarization transfer from para-hydrogen to the substrate nuclear spins. The nuclear spin lifetime of the created magnetization sets a strict upper limit on experimental timeframe. Short nuclear spin lifetimes are therefore a challenge for hyperpolarized metabolic imaging prospects. In this report we demonstrate how hyperpolarization and long nuclear spin lifetime can simultaneously be achieved in nitrogen-15 containing pyridazine and Phthalazine Derivatives by SABRE. These reflect two distinct classes of 15N2-coupled species with respect to their chemical symmetry and thus show different nuclear spin lifetime with the pyridazine Derivative having a singlet state lifetime of ca. 2.5 minutes, produced with a signal enhancement of ca. 2,700. In contrast the Phthalazine Derivative yields a superior 15,000-fold enhancement at 11.7 T but has a much shorter singlet lifetime

Gianpiero Garau - One of the best experts on this subject based on the ideXlab platform.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    Nature Neuroscience, 2012
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau, Tiziano Bandiera
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, that prevented anandamide internalization in vitro , interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB_1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs. After its release, the endocannabinoid anandamide is taken up from the synaptic cleft by internalization by neurons and astrocytes. Although several lines of evidence suggest that the anandamide uptake itself is a carrier-mediated diffusion process, the molecular identity of the transporter was unknown until now. Here Fu et al . show that anandamide uptake is mediated by a novel protein named FAAH-like anandamide transporter (FLAT) that is generated as an alternative splicing product of the fatty acid amide hydrolase-1 ( Faah ) mRNA.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    2011
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, which remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme, fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), which lacks amidase activity but binds anandamide with low micromolar affinity and facilitates its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, block these effects. Additionally, we identify a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, which prevents anandamide internalization in vitro, interrupts anandamide deactivation in vivo, and exerts profound analgesic effects in rodent models of nociceptive and inflammatory pain, which are mediated by CB1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs

Rosalia Bertorelli - One of the best experts on this subject based on the ideXlab platform.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    Nature Neuroscience, 2012
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau, Tiziano Bandiera
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, that remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), that lacked amidase activity but bound anandamide with low micromolar affinity and facilitated its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, blocked these effects. We also identified a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, that prevented anandamide internalization in vitro , interrupted anandamide deactivation in vivo and exerted profound analgesic effects in rodent models of nociceptive and inflammatory pain, which were mediated by CB_1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs. After its release, the endocannabinoid anandamide is taken up from the synaptic cleft by internalization by neurons and astrocytes. Although several lines of evidence suggest that the anandamide uptake itself is a carrier-mediated diffusion process, the molecular identity of the transporter was unknown until now. Here Fu et al . show that anandamide uptake is mediated by a novel protein named FAAH-like anandamide transporter (FLAT) that is generated as an alternative splicing product of the fatty acid amide hydrolase-1 ( Faah ) mRNA.

  • A catalytically silent FAAH-1 variant drives anandamide transport in neurons
    2011
    Co-Authors: Giovanni Bottegoni, Oscar Sasso, Rosalia Bertorelli, Walter Rocchia, Matteo Masetti, Ana Guijarro, Alessio Lodola, Andrea Armirotti, Gianpiero Garau
    Abstract:

    The endocannabinoid anandamide is removed from the synaptic space by a selective transport system, expressed in neurons and astrocytes, which remains molecularly uncharacterized. Here we describe a partly cytosolic variant of the intracellular anandamide-degrading enzyme, fatty acid amide hydrolase-1 (FAAH-1), termed FAAH-like anandamide transporter (FLAT), which lacks amidase activity but binds anandamide with low micromolar affinity and facilitates its translocation into cells. Known anandamide transport inhibitors, such as AM404 and OMDM-1, block these effects. Additionally, we identify a competitive antagonist of the interaction of anandamide with FLAT, the Phthalazine Derivative ARN272, which prevents anandamide internalization in vitro, interrupts anandamide deactivation in vivo, and exerts profound analgesic effects in rodent models of nociceptive and inflammatory pain, which are mediated by CB1 cannabinoid receptors. The results identify FLAT as a critical molecular component of anandamide transport in neural cells and a potential target for therapeutic drugs