Abstract:
:Signaling via G-protein-coupled receptors (GPCRs) is central for the function of biological systems. Many clinically used drugs target GPCRs directly or target molecules involved in GPCR signaling. As an alternative to targeting receptors directly, one could modulate signaling cascades downstream of receptor activation. In recent years, there has been substantial interest in a family of proteins called regulators of G protein signaling (RGS) proteins. They modulate GPCR signaling by accelerating GTP hydrolysis on active Galpha subunits, thereby reducing the amplitude and duration of signaling. Modulating RGS activity would be a useful strategy to control GPCR signaling. An RGS inhibitor would be expected to enhance GPCR signaling and could do so in a tissue- or pathway-specific manner. Apart from the central GAP (GTPase accelerating protein) activity, many RGS proteins also have other functions like regulating protein-protein interactions, subcellular localization of signaling molecules, and protein translation. It is clear that these proteins serve important functions in a number of physiological and pathophysiological processes, and they are emerging as potential drug targets. This chapter gives an overview of what is currently known about biological functions of RGS proteins based on in vivo and in vitro data. We also summarize the current status in targeting RGS proteins in drug discovery.
journal_name
Prog Mol Biol Transl Scijournal_title
Progress in molecular biology and translational scienceauthors
Sjögren B,Blazer LL,Neubig RRdoi
10.1016/S1877-1173(10)91004-1subject
Has Abstractpub_date
2010-01-01 00:00:00pages
81-119eissn
1877-1173issn
1878-0814pii
S1877-1173(10)91004-1journal_volume
91pub_type
杂志文章,评审abstract::In this chapter, we describe how to create mathematical models of synaptic transmission and integration. We start with a brief synopsis of the experimental evidence underlying our current understanding of synaptic transmission. We then describe synaptic transmission at a particular glutamatergic synapse in the mammali...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-397897-4.00004-8
更新日期:2014-01-01 00:00:00
abstract::Guanine nucleotide-binding proteins of the inhibitory (Gi/o) class play critical physiological roles and the receptors that activate them are important therapeutic targets (e.g., mu opioid, serotonin 5HT1a, etc.). Gi/o proteins are negatively regulated by regulator of G protein signaling (RGS) proteins. The redundant ...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2015.04.010
更新日期:2015-01-01 00:00:00
abstract::Both genetic and environmental factors play roles in the development of refractive errors. Identification of genes involved in refractive errors may help in elucidating the underlying molecular mechanism related to both genetic defects and environmental pressure. Recent development of techniques for genome wide analys...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2015.05.007
更新日期:2015-01-01 00:00:00
abstract::A wide range of neuroimmunological diseases, referred to as autoimmune neuropathies, affect the peripheral nervous systems (PNS). The PNS is structurally diverse with complex anatomical compartments enriched in many different myelin and neuronal glycolipids, notably gangliosides. Autoimmune neuropathies are a proporti...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.12.010
更新日期:2018-01-01 00:00:00
abstract::Amyloids are nanoscopic ordered self-assemblies of misfolded proteins that are formed via aggregation of partially unfolded or intrinsically disordered proteins (IDPs) and are commonly linked to devastating human diseases. An enlarging body of recent research has demonstrated that certain amyloids can be beneficial an...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2019.05.005
更新日期:2019-01-01 00:00:00
abstract::Longitudinal growth results from multifactorial and complex processes that take place in the context of different genetic traits and environmental influences. Thus, in view of the difficulties in comprehension of the physiological mechanisms involved in the achievement of normal height, our ability to make a definitiv...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2015.10.009
更新日期:2016-01-01 00:00:00
abstract::Circulating tumor cells (CTCs) can be separated and characterized from normal hematopoietic cellular constituents by a variety of methods. Different strategies have included separation by physical characteristics, such as size or weight, or by biological characteristics, such as expression of epithelial or cancer-spec...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-385071-3.00005-8
更新日期:2010-01-01 00:00:00
abstract::Glycated serum protein (GSP, measured as serum fructosamine concentration in μmol/L) is a product of glycation reaction between glucose and serum proteins in the blood circulation. GSP is used along with blood glucose, glycated hemoglobin (HbA1c), and glycated albumin as indicators of glycemic control for diabetic pat...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章
doi:10.1016/bs.pmbts.2019.01.007
更新日期:2019-01-01 00:00:00
abstract::Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The central and periph...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-396971-2.00009-9
更新日期:2013-01-01 00:00:00
abstract::In 1982, the Cech group discovered that an intron structure in an rRNA precursor of Tetrahymena thermophila is sufficient to complete splicing without assistance from proteins. This was the first moment that scientists recognized RNAs can have catalytic activities derived from their own unique three-dimensional struct...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2018.07.001
更新日期:2018-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the leading cause of dementia and sixth cause of death in elderly adults. AD poses a huge economic burden on society and constitutes an unprecedented challenge for caregivers and families affected. Aging of the population is projected to drastically aggravate the situation in the near futur...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章
doi:10.1016/bs.pmbts.2020.10.002
更新日期:2021-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the major form of dementia and a growing epidemic for which no disease-modifying treatments exist. AD is characterized by the early loss of synapses in the brain and, at later stages, neuronal death accompanied with progressive loss of cognitive functions. Here we focus on the mechanisms in...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2019.07.003
更新日期:2019-01-01 00:00:00
abstract::Attention has been focused on Wnt signaling in the mouse mammary gland for several decades, firstly by the discovery of several Wnt loci among the oncogenes revealed by MMTV-based insertional mutagenesis screening of mouse mammary gland, and then by the remarkable visualization of Wnt-dependent specification of mammar...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.11.020
更新日期:2018-01-01 00:00:00
abstract::Among the most sensitive, specific and practical of methods for detecting prions are the real-time quaking-induced conversion (RT-QuIC) assays. These assays exploit the fundamental self-propagating activity of prions to amplify the presence of prion seeds by as much as a trillion-fold. The reactions can detect most of...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.06.003
更新日期:2017-01-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.02.002
更新日期:2017-01-01 00:00:00
abstract::G protein-coupled receptors (or GPCRs) represent the largest family of membrane proteins in the human genome and are the target of approximately half of all therapeutic drugs. GPCRs contain a conserved structure of seven transmembrane domains. Their amino terminus is located extracellularly, whereas the carboxy termin...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-386931-9.00008-8
更新日期:2013-01-01 00:00:00
abstract::The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in nociceptive pathways. The chronicity of neuropathic pain therefore underscores the importance of understanding the contribution of dendritic spines--micron-s...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2014.12.001
更新日期:2015-01-01 00:00:00
abstract::Parathyroid hormone (PTH) is the principle regulator of calcium-phosphorus metabolism and bone turnover. Because of its central role in bone remodeling, recombinant human PTH (i.e., Forteo®; PTH(1-34)) has been developed for the treatment of osteoporosis. PTH(1-34) acts principally through the type I PTH/PTH-related p...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-394440-5.00013-9
更新日期:2013-01-01 00:00:00
abstract::Regulators of G protein signaling (RGS) comprise a diverse group of about 40 proteins which determine signaling amplitude and duration via modulation of receptor/G protein or receptor/effector coupling. Several members of the RGS family are expressed in the brain, where they have precise roles in regulation of importa...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/S1877-1173(09)86010-9
更新日期:2009-01-01 00:00:00
abstract::Mitochondria are well-known cellular organelles that play a vital role in cellular bioenergetics, heme biosynthesis, thermogenesis, calcium homeostasis, lipid catabolism, and other metabolic activities. Given the extensive role of mitochondria in cell function, mitochondrial dysfunction plays a part in many diseases, ...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2016.12.019
更新日期:2017-01-01 00:00:00
abstract::-1 Programmed ribosomal frameshifting is a translational recoding event in which ribosomes slip backward along messenger RNA presumably due to increased tension disrupting the codon-anticodon interaction at the ribosome's coding site. Single-molecule physical methods and recent experiments characterizing the physical ...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2015.11.003
更新日期:2016-01-01 00:00:00
abstract::Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators ...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.04.001
更新日期:2017-01-01 00:00:00
abstract::In eukaryotes, methylation of nucleosomal histones and other nuclear proteins is a central aspect of chromatin structure and dynamics. The past 15 years have seen an enormous advance in our understanding of the biochemistry of these modifications, and of their role in establishing the epigenetic code. We provide a syn...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章
doi:10.1016/B978-0-12-387685-0.00004-4
更新日期:2011-01-01 00:00:00
abstract::Grifola frondosa, a polypore fungus that grows at the base of trees, is an edible and medicinal mushroom with a large fruiting body characterized by overlapping caps. Japanese scholars found that Grifola frondosa polysaccharide or D-fraction is the major biologically active ingredient, which is a protein-bound glucan ...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2019.02.010
更新日期:2019-01-01 00:00:00
abstract::Pathologic aggregates of tau protein are observed in several neurodegenerative diseases and are used to diagnose and stage disease postmortem. Recent advances in positron emission tomography radioligands allow for the detection of aggregated tau proteins in living persons. This chapter describes the development and ch...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2019.07.007
更新日期:2019-01-01 00:00:00
abstract::Bacteriophage T4 is the archetype of virulent phage. It has evolved very efficient strategies to subvert host functions to its benefit and to impose the expression of its genome. T4 utilizes a combination of host and phage-encoded RNases and factors to degrade its mRNAs in a stage-dependent manner. The host endonuclea...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/S0079-6603(08)00802-7
更新日期:2009-01-01 00:00:00
abstract::Stem cell differentiation into a variety of lineages is known to involve signaling from the extracellular niche, including from the physical properties of that environment. What regulates stem cell responses to these cues is there ability to activate different mechanotransductive pathways. Here, we will review the str...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/B978-0-12-394624-9.00009-9
更新日期:2014-01-01 00:00:00
abstract::Obesity contributes to the aging process through the alteration of metabolic pathways evidenced biochemically in the relationship between caloric restriction and longevity. Humans have entered into an era of metabolism and aging entirely unprecedented in their evolution, with a diet that, for many, contains a majority...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2017.11.016
更新日期:2018-01-01 00:00:00
abstract::Ndsts (N-deacetylase/N-sulfotransferases) are enzymes responsible for N-sulfation during heparan sulfate (HS) and heparin biosynthesis. In this review, basic features of the Ndst1 enzyme are covered and a brief description of HS biosynthesis and its regulation is presented. Effects of Ndst1 deficiency on embryonic dev...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/S1877-1173(10)93003-2
更新日期:2010-01-01 00:00:00
abstract::Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analy...
journal_title:Progress in molecular biology and translational science
pub_type: 杂志文章,评审
doi:10.1016/bs.pmbts.2015.03.007
更新日期:2015-01-01 00:00:00