scholarly journals Optogenetics and pharmacogenetics: principles and applications

2017 ◽  
Vol 313 (6) ◽  
pp. R633-R645 ◽  
Author(s):  
Jingwei Jiang ◽  
Huxing Cui ◽  
Kamal Rahmouni
Keyword(s):  
Small Molecules ◽  
Neuronal Activity ◽  
G Protein Coupled Receptors ◽  
Designer Drug ◽  
Physiological Processes ◽  
System Neuroscience ◽  
Health And Disease ◽  
Bidirectional Modulation ◽  
Spatiotemporal Control ◽  
G Protein Coupled

Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics. The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity. These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease. Here, we discuss the fundamental elements of optogenetics and chemogenetics approaches and some of the applications that yielded significant advances in various areas of neuroscience and beyond.

scholarly journals Bovine Serum Albumin-Estrogen Compounds Differentially Alter Gonadotropin-Releasing Hormone-1 Neuronal Activity

Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 558-563 ◽  
Author(s):  
Jennifer L. Temple ◽  
Susan Wray
Keyword(s):  
Steroid Hormones ◽  
Gene Transcription ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Binding Properties ◽  
Physiological Processes ◽  
17Β Estradiol ◽  
G Protein Coupled

Abstract Steroid hormones regulate a host of physiological processes and behaviors. These actions can occur by genomic mechanisms involving gene transcription or by nongenomic mechanisms proposed to involve receptors associated with the plasma membrane. BSA-conjugated steroid hormones have been extensively used to elucidate signal transduction pathways for these hormones. We have previously shown, using calcium imaging, that 17β-estradiol (E2) significantly increases GnRH-1 neuronal activity. During the course of these experiments, it became apparent that three different BSA-estrogen compounds have been used in a variety of cell types: 17β-estradiol 6-O-carboxymethyloxime-BSA (E2-6-BSA); 1,3,5(10)-estratrien-3,16α,17β-triol-6-one 6-O-carboxymethyloxime-BSA (E-6-BSA); and 1,3,5(10)-estratrien-3,17β-diol 17-hemisuccinate-BSA (E2-17-BSA). The effects of these compounds on GnRH-1 neuronal activity were compared using calcium imaging. E-6-BSA and E2-17-BSA, but not E2-6-BSA, significantly increased all parameters of GnRH-1 neuronal activity. In addition, the effects of these two BSA compounds were reversed by the estrogen receptor antagonist ICI 182,780 but not by inhibition of gene transcription. The effects of E2-17-BSA, but not E-6-BSA were reversed by treatment with pertussis toxin, which blocks G protein-coupled receptors. These data indicate that these compounds cannot be used interchangeably and clearly have different binding properties and/or different effects on target tissues.

scholarly journals Adhesion GPCRs in Glioblastoma

2021 ◽  
Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Past ◽  
Novel Treatment ◽  
The Family ◽  
Health And Disease ◽  
Basic Biology ◽  
G Protein Coupled ◽  
Potential Use ◽  
Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

scholarly journals Mini-review: antibody therapeutics targeting G protein-coupled receptors and ion channels

2020 ◽  
Vol 3 (4) ◽  
pp. 257-264
Author(s):  
Catherine J Hutchings
Keyword(s):  
Ion Channels ◽  
Research And Development ◽  
Small Molecules ◽  
G Protein ◽  
Clinical Studies ◽  
G Protein Coupled Receptors ◽  
Protein Targets ◽  
Antibody Therapeutics ◽  
Wide Range ◽  
G Protein Coupled

Abstract Antibodies are now well established as therapeutics with many additional advantages over small molecules and peptides relative to their selectivity, bioavailability, half-life and effector function. Major classes of membrane-associated protein targets include G protein-coupled receptors (GPCRs) and ion channels that are linked to a wide range of disease indications across all therapeutic areas. This mini-review summarizes the antibody target landscape for both GPCRs and ion channels as well as current progress in the respective research and development pipelines with some example case studies highlighted from clinical studies, including those being evaluated for the treatment of symptoms in COVID-19 infection.

scholarly journals Applications of molecular replacement to G protein-coupled receptors

2013 ◽  
Vol 69 (11) ◽  
pp. 2287-2292 ◽  
Author(s):  
Andrew C. Kruse ◽  
Aashish Manglik ◽  
Brian K. Kobilka ◽  
William I. Weis
Keyword(s):  
G Protein ◽  
Structural Biology ◽  
Structural Information ◽  
G Protein Coupled Receptors ◽  
Integral Membrane Proteins ◽  
Molecular Replacement ◽  
Gpcr Activation ◽  
Health And Disease ◽  
Almost All ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are a large class of integral membrane proteins involved in regulating virtually every aspect of human physiology. Despite their profound importance in human health and disease, structural information regarding GPCRs has been extremely limited until recently. With the advent of a variety of new biochemical and crystallographic techniques, the structural biology of GPCRs has advanced rapidly, offering key molecular insights into GPCR activation and signal transduction. To date, almost all GPCR structures have been solved using molecular-replacement techniques. Here, the unique aspects of molecular replacement as applied to individual GPCRs and to signaling complexes of these important proteins are discussed.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

Identification Methods of G Protein-Coupled Receptors

2011 ◽  
Vol 2 (4) ◽  
pp. 35-52
Author(s):  
Meriem Zekri ◽  
Karima Alem ◽  
Labiba Souici-Meslati
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Pharmaceutical Research ◽  
G Protein Coupled Receptors ◽  
Machine Learning Algorithms ◽  
Signaling Networks ◽  
Identification Methods ◽  
Physiological Processes ◽  
Cell Signaling Networks ◽  
G Protein Coupled

The G protein-coupled receptors (GPCRs) include one of the largest and most important families of multifunctional proteins known to molecular biology. They play a key role in cell signaling networks that regulate many physiological processes, such as vision, smell, taste, neurotransmission, secretion, immune responses, metabolism, and cell growth. These proteins are thus very important for understanding human physiology and they are involved in several diseases. Therefore, many efforts in pharmaceutical research are to understand their structures and functions, which is not an easy task, because although thousands GPCR sequences are known, many of them remain orphans. To remedy this, many methods have been developed using methods such as statistics, machine learning algorithms, and bio-inspired approaches. In this article, the authors review the approaches used to develop algorithms for classification GPCRs by trying to highlight the strengths and weaknesses of these different approaches and providing a comparison of their performances.

scholarly journals Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae)

2018 ◽  
Vol 19 (12) ◽  
pp. 3912 ◽  
Author(s):  
Zhengbing Wang ◽  
Wenwu Zhou ◽  
Muhammad Hameed ◽  
Jiali Liu ◽  
Xinnian Zeng
Keyword(s):  
G Protein ◽  
Developmental Stages ◽  
G Protein Coupled Receptors ◽  
Nerve Tissue ◽  
Asian Citrus Psyllid ◽  
Diaphorina Citri ◽  
Physiological Processes ◽  
Neuropeptide Receptors ◽  
G Protein Coupled ◽  
Active Substances

Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.

Unravelling the mechanisms underpinning chemokine receptor activation and blockade by small molecules: a fine line between agonism and antagonism?

2007 ◽  
Vol 35 (4) ◽  
pp. 755-759 ◽  
Author(s):  
E. Wise ◽  
J.E. Pease
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Considerable Effort ◽  
G Protein Coupled ◽  
Migration Of Cells

Chemokines are a family of small basic proteins which induce the directed migration of cells, notably leucocytes, by binding to specific GPCRs (G-protein-coupled receptors). Both chemokines and their receptors have been implicated in a host of clinically important diseases, leading to the notion that antagonism of the chemokine–chemokine receptor network may be therapeutically advantageous. Consequently, considerable effort has been put into the development of small-molecule antagonists of chemokine receptors and several such compounds have been described in the literature. One curious by-product of this activity has been the description of several small-molecule agonists of the receptors, which are typically discovered following the optimization of lead antagonists. In this review we discuss these findings and conclude that these small-molecule agonists might be exploited to further our understanding of the molecular mechanisms by which chemokine receptors are activated.

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