G Protein-Coupled Receptor Heteromers as Putative Pharmacotherapeutic Targets in Autism.

Abstract:

:A major challenge in the development of pharmacotherapies for autism is the failure to identify pathophysiological mechanisms that could be targetable. The majority of developing strategies mainly aim at restoring the brain excitatory/inhibitory imbalance described in autism, by targeting glutamate or GABA receptors. Other neurotransmitter systems are critical for the fine-tuning of the brain excitation/inhibition balance. Among these, the dopaminergic, oxytocinergic, serotonergic, and cannabinoid systems have also been implicated in autism and thus represent putative therapeutic targets. One of the latest breakthroughs in pharmacology has been the discovery of G protein-coupled receptor (GPCR) oligomerization. GPCR heteromers are macromolecular complexes composed of at least two different receptors, with biochemical properties that differ from those of their individual components, leading to the activation of different cellular signaling pathways. Interestingly, heteromers of the above-mentioned neurotransmitter receptors have been described (e.g., mGlu2-5HT2A, mGlu5-D2-A2A, D2-OXT, CB1-D2, D2-5HT2A, D1-D2, D2-D3, and OXT-5HT2A). We hypothesize that differences in the GPCR interactome may underlie the etiology/pathophysiology of autism and could drive different treatment responses, as has already been suggested for other brain disorders such as schizophrenia. Targeting GPCR complexes instead of monomers represents a new order of biased agonism/antagonism that may potentially enhance the efficacy of future pharmacotherapies. Here, we present an overview of the crosstalk of the different GPCRs involved in autism and discuss current advances in pharmacological approaches targeting them.

journal_name

Front Cell Neurosci

authors

DelaCuesta-Barrutia J,Peñagarikano O,Erdozain AM

doi

10.3389/fncel.2020.588662

subject

Has Abstract

pub_date

2020-10-30 00:00:00

pages

588662

issn

1662-5102

journal_volume

14

pub_type

杂志文章,评审
  • The Molecular Determinants of Mitochondrial Membrane Contact With ER, Lysosomes and Peroxisomes in Neuronal Physiology and Pathology.

    abstract::Membrane tethering is an important communication method for membrane-packaged organelles. Mitochondria are organelles with a bilayer membrane, and the membrane contact between mitochondria and other organelles is indispensable for maintaining cellular homeostasis. Increased levels of molecular determinants that mediat...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.00194

    authors: Liao Y,Dong Y,Cheng J

    更新日期:2020-08-07 00:00:00

  • ER stress and unfolded protein response in amyotrophic lateral sclerosis-a controversial role of protein disulphide isomerase.

    abstract::Accumulation of proteins in aberrant conformation occurs in many neurodegenerative diseases. Furthermore, dysfunctions in protein handling in endoplasmic reticulum (ER) and the following ER stress have been implicated in a vast number of diseases, such as amyotrophic lateral sclerosis (ALS). During excessive ER stress...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2014.00402

    authors: Jaronen M,Goldsteins G,Koistinaho J

    更新日期:2014-12-02 00:00:00

  • Diversity of layer 5 projection neurons in the mouse motor cortex.

    abstract::In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolv...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2013.00174

    authors: Oswald MJ,Tantirigama ML,Sonntag I,Hughes SM,Empson RM

    更新日期:2013-10-16 00:00:00

  • Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat.

    abstract::The present study was designed to observe the effect of COX2/PGD2-related autophagy on brain injury in type 2 diabetes rats. The histopathology was detected by haematoxylin-eosin staining. The learning and memory functions were evaluated by Morris water maze. The levels of insulin and PGD2 were measured by enzyme-link...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00068

    authors: Yang Y,Chen Q,Zhao Q,Luo Y,Xu Y,Du W,Wang H,Li H,Yang L,Hu C,Zhang J,Li Y,Xia H,Chen Z,Ma J,Tian X,Yang J

    更新日期:2019-02-27 00:00:00

  • Mild Endoplasmic Reticulum Stress Protects Against Lipopolysaccharide-Induced Astrocytic Activation and Blood-Brain Barrier Hyperpermeability.

    abstract::Recent research has revealed that uncontrolled chronic neuroinflammation is closely associated with diverse neurodegenerative diseases, by impairing blood-brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER) stress is conventionally linked to the loss of neuronal structure and function and ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00222

    authors: Wang Y,Chen Y,Zhou Q,Xu J,Qian Q,Ni P,Qian Y

    更新日期:2018-07-27 00:00:00

  • The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1.

    abstract::After damage, axons in the peripheral nervous system (PNS) regenerate and regrow following a process termed Wallerian degeneration, but the regenerative process is often incomplete and usually the system does not reach full recovery. Key steps to the creation of a permissive environment for axonal regrowth are the tra...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2019.00093

    authors: Pellegatta M,Taveggia C

    更新日期:2019-03-20 00:00:00

  • Neuromodulation of Glial Function During Neurodegeneration.

    abstract::Glia, a non-excitable cell type once considered merely as the connective tissue between neurons, is nowadays acknowledged for its essential contribution to multiple physiological processes including learning, memory formation, excitability, synaptic plasticity, ion homeostasis, and energy metabolism. Moreover, as glia...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.00278

    authors: Stevenson R,Samokhina E,Rossetti I,Morley JW,Buskila Y

    更新日期:2020-08-21 00:00:00

  • Motor and Cerebellar Architectural Abnormalities during the Early Progression of Ataxia in a Mouse Model of SCA1 and How Early Prevention Leads to a Better Outcome Later in Life.

    abstract::Exposing developing cerebellar Purkinje neurons (PNs) to mutant Ataxin1 (ATXN1) in 82Q spinocerebellar ataxia type 1 (SCA1) mice disrupts motor behavior and cerebellar climbing fiber (CF) architecture from as early as 4 weeks of age. In contrast, if mutant ATXN1 expression is silenced until after cerebellar developmen...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00292

    authors: Ibrahim MF,Power EM,Potapov K,Empson RM

    更新日期:2017-09-20 00:00:00

  • Matrix metalloproteinase 9 (MMP-9) is indispensable for long term potentiation in the central and basal but not in the lateral nucleus of the amygdala.

    abstract::It has been shown that matrix metalloproteinase 9 (MMP-9) is required for synaptic plasticity, learning and memory. In particular, MMP-9 involvement in long-term potentiation (LTP, the model of synaptic plasticity) in the hippocampus and prefrontal cortex has previously been demonstrated. Recent data suggest the role ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2015.00073

    authors: Gorkiewicz T,Balcerzyk M,Kaczmarek L,Knapska E

    更新日期:2015-03-11 00:00:00

  • Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.

    abstract::Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca(2+) buffers that shape [Ca(2+)] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca(2+) faster than any other character...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2015.00239

    authors: Timofeeva Y,Volynski KE

    更新日期:2015-07-01 00:00:00

  • TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect.

    abstract::Thyrotropin-releasing hormone (TRH) and its analogs are able to stimulate the release of the endogenic dopamine (DA) in the central nervous system. However, this effect has not been tested in the Parkinson's disease (PD), which is characterized by the DA deficiency due to the dopaminergic neurons loss in the substanti...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00417

    authors: Zheng C,Chen G,Tan Y,Zeng W,Peng Q,Wang J,Cheng C,Yang X,Nie S,Xu Y,Zhang Z,Papa SM,Ye K,Cao X

    更新日期:2018-11-13 00:00:00

  • Developmental changes in GABAergic mechanisms in human visual cortex across the lifespan.

    abstract::Functional maturation of visual cortex is linked with dynamic changes in synaptic expression of GABAergic mechanisms. These include setting the excitation-inhibition balance required for experience-dependent plasticity, as well as, intracortical inhibition underlying development and aging of receptive field properties...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2010.00016

    authors: Pinto JG,Hornby KR,Jones DG,Murphy KM

    更新日期:2010-06-10 00:00:00

  • Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice.

    abstract::The etiology of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5-10% of cases are familial, and of those, 15-20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2016.00117

    authors: Juranek JK,Daffu GK,Geddis MS,Li H,Rosario R,Kaplan BJ,Kelly L,Schmidt AM

    更新日期:2016-05-09 00:00:00

  • Role of satellite glial cells in gastrointestinal pain.

    abstract::Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2015.00412

    authors: Hanani M

    更新日期:2015-10-13 00:00:00

  • The NMDA receptor complex: a multifunctional machine at the glutamatergic synapse.

    abstract::The N-methyl-D-aspartate receptors (NMDARs) are part of a large multiprotein complex at the glutamatergic synapse. The assembly of NMDARs with synaptic proteins offers a means to regulate NMDAR channel properties and receptor trafficking, and couples NMDAR activation to distinct intracellular signaling pathways, thus ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2014.00160

    authors: Fan X,Jin WY,Wang YT

    更新日期:2014-06-10 00:00:00

  • Dye Tracking Following Posterior Semicircular Canal or Round Window Membrane Injections Suggests a Role for the Cochlea Aqueduct in Modulating Distribution.

    abstract::The inner ear houses the sensory epithelium responsible for vestibular and auditory function. The sensory epithelia are driven by pressure and vibration of the fluid filled structures in which they are embedded so that understanding the homeostatic mechanisms regulating fluid dynamics within these structures is critic...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00471

    authors: Talaei S,Schnee ME,Aaron KA,Ricci AJ

    更新日期:2019-10-30 00:00:00

  • Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress.

    abstract::Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK) production contributes to the increased transport through the blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00333

    authors: Arredondo Zamarripa D,Díaz-Lezama N,Meléndez García R,Chávez Balderas J,Adán N,Ledesma-Colunga MG,Arnold E,Clapp C,Thebault S

    更新日期:2014-10-20 00:00:00

  • JNK1 controls dendritic field size in L2/3 and L5 of the motor cortex, constrains soma size, and influences fine motor coordination.

    abstract::Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia, and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00272

    authors: Komulainen E,Zdrojewska J,Freemantle E,Mohammad H,Kulesskaya N,Deshpande P,Marchisella F,Mysore R,Hollos P,Michelsen KA,Mågard M,Rauvala H,James P,Coffey ET

    更新日期:2014-09-12 00:00:00

  • Activated PPARγ Abrogates Misprocessing of Amyloid Precursor Protein, Tau Missorting and Synaptotoxicity.

    abstract::Type 2 diabetes increases the risk for dementia, including Alzheimer's disease (AD). Pioglitazone (Pio), a pharmacological agonist of the peroxisome proliferator-activated receptor γ (PPARγ), improves insulin sensitivity and has been suggested to have potential in the management of AD symptoms, albeit through mostly u...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00239

    authors: Moosecker S,Gomes P,Dioli C,Yu S,Sotiropoulos I,Almeida OFX

    更新日期:2019-06-12 00:00:00

  • A Sex Pheromone Receptor in the Hessian Fly Mayetiola destructor (Diptera, Cecidomyiidae).

    abstract::The Hessian fly, Mayetiola destructor Say (Diptera, Cecidomyiidae), is a pest of wheat and belongs to a group of gall-inducing herbivores. This species has a unique life history and several ecological features that differentiate it from other Diptera such as Drosophila melanogaster and blood-feeding mosquitoes. These ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2016.00212

    authors: Andersson MN,Corcoran JA,Zhang DD,Hillbur Y,Newcomb RD,Löfstedt C

    更新日期:2016-09-07 00:00:00

  • Purple Corn Extract as Anti-allodynic Treatment for Trigeminal Pain: Role of Microglia.

    abstract::Natural products have attracted interest in the search for new and effective analgesics and coadjuvant approaches to several types of pain. It is in fact well known that many of their active ingredients, such as anthocyanins (ACNs) and polyphenols, can exert potent anti-inflammatory actions. Nevertheless, their potent...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00378

    authors: Magni G,Marinelli A,Riccio D,Lecca D,Tonelli C,Abbracchio MP,Petroni K,Ceruti S

    更新日期:2018-11-05 00:00:00

  • Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization.

    abstract::The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizin...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2015.00047

    authors: Masoli S,Solinas S,D'Angelo E

    更新日期:2015-02-24 00:00:00

  • Firing Frequency Maxima of Fast-Spiking Neurons in Human, Monkey, and Mouse Neocortex.

    abstract::Cortical fast-spiking (FS) neurons generate high-frequency action potentials (APs) without apparent frequency accommodation, thus providing fast and precise inhibition. However, the maximal firing frequency that they can reach, particularly in primate neocortex, remains unclear. Here, by recording in human, monkey, an...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2016.00239

    authors: Wang B,Ke W,Guang J,Chen G,Yin L,Deng S,He Q,Liu Y,He T,Zheng R,Jiang Y,Zhang X,Li T,Luan G,Lu HD,Zhang M,Zhang X,Shu Y

    更新日期:2016-10-18 00:00:00

  • Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus.

    abstract::The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (K...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2011.00023

    authors: Khalilov I,Chazal G,Chudotvorova I,Pellegrino C,Corby S,Ferrand N,Gubkina O,Nardou R,Tyzio R,Yamamoto S,Jentsch TJ,Hübner CA,Gaiarsa JL,Ben-Ari Y,Medina I

    更新日期:2011-11-01 00:00:00

  • Drebrin Isoforms Critically Regulate NMDAR- and mGluR-Dependent LTD Induction.

    abstract::Drebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during development. In parallel,...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00330

    authors: Yasuda H,Kojima N,Hanamura K,Yamazaki H,Sakimura K,Shirao T

    更新日期:2018-10-08 00:00:00

  • Antiphospholipid Antibodies Overlapping in Isolated Neurological Syndrome and Multiple Sclerosis: Neurobiological Insights and Diagnostic Challenges.

    abstract::Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and n...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00107

    authors: D'Angelo C,Franch O,Fernández-Paredes L,Oreja-Guevara C,Núñez-Beltrán M,Comins-Boo A,Reale M,Sánchez-Ramón S

    更新日期:2019-03-19 00:00:00

  • Advances in the Signaling Pathways Downstream of Glial-Scar Axon Growth Inhibitors.

    abstract::Axon growth inhibitors generated by reactive glial scars play an important role in failure of axon regeneration after CNS injury in mature mammals. Among the inhibitory factors, chondroitin sulfate proteoglycans (CSPGs) are potent suppressors of axon regeneration and are important molecular targets for designing effec...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2020.00174

    authors: Sami A,Selzer ME,Li S

    更新日期:2020-07-02 00:00:00

  • Heritable and inducible gene knockdown in astrocytes or neurons in vivo by a combined lentiviral and RNAi approach.

    abstract::Gene knockout by homologous recombination is a popular method to study gene functions in the mouse in vivo. However, its lack of temporal control has limited the interpretation of knockout studies because the complete elimination of a gene product often alters developmental processes, and can induce severe malformatio...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00062

    authors: Heitz F,Johansson T,Baumgärtel K,Gecaj R,Pelczar P,Mansuy IM

    更新日期:2014-03-19 00:00:00

  • Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.

    abstract::The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging t...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00107

    authors: Zhao R,Zhou H,Huang L,Xie Z,Wang J,Gan WB,Yang G

    更新日期:2018-04-20 00:00:00

  • Enhanced Axonal Extension of Subcortical Projection Neurons Isolated from Murine Embryonic Cortex using Neuropilin-1.

    abstract::The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)-derived neurons can survive in the brain and extend axons to the spinal cord. For efficient cell integration to the corticospinal tract (CST) after transplantation, the induction or selection of cortical motor neurons is important. However, ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00123

    authors: Sano N,Shimogawa T,Sakaguchi H,Ioroi Y,Miyawaki Y,Morizane A,Miyamoto S,Takahashi J

    更新日期:2017-05-01 00:00:00