Francine C Acher

Francine C Acher
Paris Descartes, CPSC | Paris 5 · Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (CNRS-UMR8601)

PhD

About

196
Publications
11,605
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5,394
Citations
Citations since 2016
32 Research Items
1883 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300

Publications

Publications (196)
Preprint
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In addition to its well-known receptor-mediated function in cell survival, differentiation and growth, we report that the extracellular brain-derived neurotrophic factor (BDNF) also controls the intracellular KEAP1-NRF2 cytoprotective system by a receptor-independent pathway. Extracellular BDNF can cross the cell membrane as it possesses a protein-...
Article
Metabotropic glutamate receptors (mGluRs) have been discovered almost four decades ago. Since then, their pharmacology has been largely developed as well as their structural organization. Indeed mGluRs are attractive therapeutic targets for numerous psychiatric and neurological disorders because of their modulating role of synaptic transmission. Th...
Article
Full-text available
Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Metabotropic Glutamate Receptors [347]) are a family of G protein-coupled receptors activated by the neurotransmitter glutamate [138]. The mGlu family is composed of eight members (named mGlu1 to mGlu8) which are divided in three groups based on similar...
Article
Significance Biologics, and especially antibodies, are promising therapeutics. Antibodies are expected to show higher subtype selectivity and less off-target activity than small molecules. G protein–coupled receptors (GPCRs) being the main drug targets, there is a need for antibodies modulating these receptors. Here, we describe the first single-do...
Article
Cocaine addiction is a serious health issue in Western countries. Despite the regular increase in cocaine consumption across the population, there is no specific treatment for cocaine addiction. Critical roles for glutamate neurotransmission in the rewarding effects of psychostimulants as well as relapse have been suggested and accumulating evidenc...
Article
Full-text available
Significance G protein-coupled receptors regulate several physiological processes, many of which sense nutrients. The mode of action of these nutrients remains elusive, as it is difficult to control nutrient concentrations around living cells. The calcium-sensing receptor is regulated by multiple factors, including ions and amino acids, to control...
Article
Sialin is a lysosomal sialic acid transporter defective in Salla disease, a rare inherited leukodystrophy. It also enables metabolic incorporation of exogenous sialic acids, leading to autoantibodies against N-glycolylneuraminic acid in humans. Here we identified a novel class of human sialin ligands by virtual screening and structure-activity rela...
Article
Full-text available
Current antidepressants act principally by blocking monoamine reuptake by high-affinity transporters in the brain. However, these antidepressants show important shortcomings such as slow action onset and limited efficacy in nearly a third of patients with major depression disorder. Here, we report the development of a prodrug targeting organic cati...
Article
Full-text available
The alanine-serine-cysteine transporter Asc-1 regulates the synaptic availability of d-serine and glycine (the two co-agonists of the NMDA receptor) and is regarded as an important drug target. To shuttle the substrate from the extracellular space to the cytoplasm, this transporter undergoes multiple distinct conformational states. In this work, ho...
Article
Full-text available
Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity ~4000-fold lower than other mGluRs and a maximal activation of onl...
Article
Vesicular glutamate transporters (VGLUT1-3) mediate the uptake of glutamate into synaptic vesicles. VGLUTs are pivotal actors of excitatory transmission and of almost all brain functions. Their implication in various pathologies has been clearly documented. Despite their functional importance, the pharmacology of VGLUTs is limited to a few dyes suc...
Article
Full-text available
The glutamate metabotropic receptor 4 (GRM4) locus is linked to susceptibility to human osteosarcoma, through unknown mechanisms. We show that Grm4−/− gene–targeted mice demonstrate accelerated radiation-induced tumor development to an extent comparable with Rb1+/− mice. GRM4 is expressed in myeloid cells, selectively regulating expression of IL23...
Article
Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Metabotropic Glutamate Receptors [334]) are a family of G protein-coupled receptors activated by the neurotransmitter glutamate. The mGlu family is composed of eight members (named mGlu1 to mGlu8) which are divided in three groups based on similarities...
Article
Finding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures.We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency on...
Preprint
Finding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures. We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency o...
Article
Full-text available
Rationale: Metabotropic glutamate receptors and muscarinic M4 receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to Go/i proteins and are expressed in brain circuits that are important in schizophrenia. Therefore, their mutual activation may be an effective treatment and a...
Article
Group-III metabotropic glutamate (mGlu) receptors are important synaptic regulators and are potential druggable targets for Parkinson disease, autism and pain. Potential drugs include orthosteric agonists in the glutamate binding extracellular domain and positive allosteric modulators interacting with seven-pass transmembrane domains. Orthosteric a...
Article
Due to the essential roles of glutamate, detection and response to a large range of extracellular concentrations of this excitatory amino acid are necessary for the fine-tuning of brain functions. Metabotropic glutamate receptors (mGluRs) are implicated in shaping the activity of many synapses in the central nervous system. Among the eight mGluR su...
Chapter
Glutamate is the major excitatory neurotransmitter of the mammalian central nervous system (CNS). Its actions are mediated by two broad classes of receptors: ligand-gated ion channels and G-protein-coupled receptors (GPCRs), named ionotropic and metabotropic glutamate receptors (mGluRs), respectively. The mGluR family consists of eight subtypes whi...
Article
A group-III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an L-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the dis...
Article
Opiate dependence is a major health issue and despite the existence of opioid substitution treatment, relapse frequently occurs. Group III metabotropic glutamate (mGlu) receptors has received much attention as a putative target in ethanol and cocaine addiction, but no data on opiate addiction exist. So we investigated the role of group III mGlu rec...
Article
Full-text available
Contrary to acute pain, chronic pain does not serve as a warning signal and must be considered as a disease per se. This pathology presents a sensory and psychological dimension at the origin of affective and cognitive disorders. Being largely refractory to current pharmacotherapies, identification of endogenous systems involved in persistent and c...
Article
Full-text available
Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence-like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics and pharmacology we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We foun...
Article
Metabotropic glutamate receptors (mGluRs) play key roles in the modulation of many synapses. Chloride (Cl(-)) is known to directly bind and regulate the function of different actors of neuronal activity, and several studies have pointed to the possible modulation of mGluRs by Cl(-). Herein, we demonstrate that Cl(-) behaves as a positive allosteric...
Article
Full-text available
Because ligands of metabotropic glutamate and GABA receptors may exert beneficial effects in schizophrenia, we have assessed the actions of the first mGlu4-selective orthosteric agonist, LSP4-2022in several tests reflecting positive, negative and cognitive symptoms of schizophrenia, and we investigated the possible involvement of GABAB receptors in...
Patent
The present invention relates to multiphoton activable organic compounds responding to the following formula (I). The present invention also relates to a method of synthesizing the compounds of the invention, to an aqueous solution comprising at least one compound of the invention, and to their specific uses. The present invention also concerns a m...
Article
Highly efficient, synthetic procedure for bis-(α-hydroxyalkyl)phosphinic acids is described using N-O-bis( trimethylsilyl)acetamide (BSA). Various substituted aldehydes undergo the addition of hypophosphorous acid in good to excellent yields. Operational simplicity, high yield and shorter reaction time are the key features associated with this prot...
Article
High two-photon photolysis cross sections and water solubility of probes are important to avoid toxicity in biomedical applications of photolysis. Systematic variation of the position of a carboxyl electron-withdrawing group (EWG) on photolysis of 8-dimethylaminoquinoline protecting groups identified the C5-substituted isomer as a privileged dipole...
Article
Metabotropic glutamate receptors (mGluRs) modulate neurotransmission all along the pain neuraxis. While the involvement of group I and group II mGluRs in pain is well documented, information has only just started to emerge concerning the role and contribution of group III mGluRs subtypes to pain modulation. Recent data suggest that these receptors...
Article
Full-text available
A series of phosphinic glutamate derivatives (e.g.) have been proven to be potent agonists of metabotropic glutamate (mGlu) receptors and shown promising in vivo activity. However, so far all were synthesized and tested as a mixture of two diastereomers whose absolute and relative configurations are not known. In this study, the stereomers were sep...
Article
Full-text available
Orthologous Cys-loop glutamate-gated chloride channels (GluClR's) have been cloned and described electrophysiologically and pharmacologically in arthropods and nematodes (both members of the invertebrate ecdysozoan superphylum). Recently, GluClR's from Aplysia californica (a mollusc from the lophotrochozoan superphylum) have been cloned and similar...
Article
Metabotropic glutamate receptor 7 (mGlu7) is a member of the group III mGlu receptors (mGlus), encompassed by mGlu4, mGlu6, mGlu7, and mGlu8. mGlu7 is highly expressed in the presynaptic active zones of both excitatory and inhibitory synapses and activation of the receptor regulates the release of both glutamate and GABA. mGlu7 is thought to be a r...
Data
The 2-methylglutamic acid (2M) analogue was generally inactive in electrophysiological experiments and had generally worse functional activity. The low functional activity obtained with 2M would not be determined by only R substitution or C methylation, since the extensive biological studies of R,R′-dialkyl cyclic analogues of glutamic acid contain...
Article
LSP1-2111 is a group III metabotropic glutamate receptor agonist with preference toward the mGlu4 receptor subtype. This compound has been extensively used as a tool to explore the pharmacology of mGlu4 receptor activation in preclinical animal behavioral models. However, the blood−brain barrier penetration of this amino acid derivative has never b...
Article
Full-text available
Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. W...
Article
Full-text available
Tandem systems allowing enhanced two-photon (2P) absorption in a wavelength range permitting coupling of the primary excitation by energy transfer to an intramolecular cage known to have fragmentation properties suited to photolysis in neuroscience is demonstrated to lead to a 10-fold improvement in the 2P photolysis cross-section at experimentally...
Article
Full-text available
Rationale Several studies have suggested that modulation of the glutamatergic system via metabotropic glutamate receptors (mGlu) could be a new way to achieve antipsychotic-like activity. LSP1-2111, the group III mGlu receptor orthosteric agonist, with a high affinity towards mGlu4 receptors, was previously shown to exhibit antipsychotic-like actio...
Article
In this issue of Structure, Lomash and colleagues report on the crystal structure and ligand binding properties of a primitive eukaryote glutamate-gated ion channel: AvGluR1.
Article
The systematic SAR study of a "caging" group showed a strong influence of the position of the donor dimethylamino group on the efficiency of photolysis of the DMAQ (2-hydroxymethylene-(N,N-dimethylamino)quinoline) caged acetate under one-photon near-UV or two-photon near-IR excitation. Photorelease of l-glutamate by the most efficient 8-DMAQ deriva...
Article
In order to deprotect N-carbobenzoxy-l-aminoacids (Cbz-AA) and related compounds, a series of microorganisms was selected from soil by enrichment cultures with Cbz-l-Glu as sole nitrogen source. A lyophilized whole-cell preparation of two Arthrobacter sp. strains grown on Cbz-Glu or Cbz-Gly exhibited a high cleavage activity. The conditions of hydr...
Article
Full-text available
A series of dicarboxylic quinoline derivatives bearing electron-releasing or -withdrawing substituents have been synthesized using mono- or/and biphasic methodologies. By controlling the regioselectivity of addition into our electrophilic intermediate, we also characterized by which mechanism the Doebner-Miller cyclization step occurred. As anticip...