Abstract:
:Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an enigmatic etiology. Family studies have strongly indicated that genetic risk factors have a role in this disease. Recent findings, together with previously established evidence, highlight the PDZ-domain-containing protein interacting with C-kinase 1 (PICK1) as a promising candidate for a schizophrenia susceptibility gene. Here, we outline possible molecular mechanisms, discuss clinical case-studies that indicate an unexpected role of PICK1 in schizophrenia and discuss potential avenues for pharmacological manipulation of PICK1.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Dev KK,Henley JMdoi
10.1016/j.tips.2006.09.007subject
Has Abstractpub_date
2006-11-01 00:00:00pages
574-9issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(06)00227-6journal_volume
27pub_type
杂志文章,评审abstract::K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00080-4
更新日期:2003-05-01 00:00:00
abstract::Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, STI571), which is used to treat chronic myeloid leukemia (CML). A recent article present...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2007.03.003
更新日期:2007-05-01 00:00:00
abstract::Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on pharmacological strategies that attack RTT treatment from multiple angles, including drug repurposing and de novo discovery efforts, and discusses the imp...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.02.007
更新日期:2019-04-01 00:00:00
abstract::Parkinson's disease (PD) is a progressive neurodegenerative disorder. Although therapies that treat the symptoms of the disease have proven efficacy, strategies that slow or stop the neurodegenerative process are currently not available. Recently, the National Institute of Neurological Disorders and Stroke (NINDS) con...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.03.003
更新日期:2004-05-01 00:00:00
abstract::It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.10.008
更新日期:2004-12-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) are involved in almost every (patho)physiological process, which explains their importance as drug targets. GPCRs have long been regarded as on/off-switches, which is reflected by direct activation or blockade of these receptors through the majority of marketed GPCR drugs. In recent...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2014.10.002
更新日期:2014-12-01 00:00:00
abstract::Although an established regulator of many cellular functions, the phosphoinositide phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2) appears to have evaded the attention of drug-discovery companies. An increasing number of reports have identified potential links between PtdIns(4,5)P2-mediated signalling pathways...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.10.004
更新日期:2005-12-01 00:00:00
abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.02.001
更新日期:2013-04-01 00:00:00
abstract::It has been over 50years since Sir James Black developed the first beta adrenergic receptor (βAR) blocker to treat heart disease. At that time, the concept of cell surface receptors was relatively new and not widely accepted, and most of the tools currently used to characterize plasma membrane receptors had not been d...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2011.02.005
更新日期:2011-04-01 00:00:00
abstract::Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2019.04.015
更新日期:2019-07-01 00:00:00
abstract::In drug development, major resources are invested into the development of cellular delivery systems to increase the effectiveness of a large array of potential therapeutics, such as proteins and oligonucleotides. These carriers comprise cell-penetrating peptides (CPPs), cationic lipids and cationic polymers. In recent...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.11.005
更新日期:2011-02-01 00:00:00
abstract::Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a dif...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.08.005
更新日期:2010-11-01 00:00:00
abstract::A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-dire...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.05.005
更新日期:2015-08-01 00:00:00
abstract::Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01249-8
更新日期:1998-10-01 00:00:00
abstract::Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less....
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/s0165-6147(02)02007-2
更新日期:2002-05-01 00:00:00
abstract::Erythropoietin (EPO) has emerged as a versatile growth factor that has transcended its traditional role as a mediator of erythroid maturation to one that modulates stem cell development, cellular protection and angiogenesis in the brain. As a possible candidate for nervous system disorders, it becomes crucial to under...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.09.006
更新日期:2004-11-01 00:00:00
abstract::In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01413-3
更新日期:2000-01-01 00:00:00
abstract::Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.12.005
更新日期:2011-03-01 00:00:00
abstract::Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.05.006
更新日期:2017-08-01 00:00:00
abstract::Complete nucleotide sequences are now available for different species of the animal kingdom: Caenorhabditis elegans - a nematode, Drosophila - an insect, and humans - a mammal. Such information makes it possible to compare the set of nuclear receptors found in these organisms, and to discuss the possible reasons for t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01859-9
更新日期:2001-12-01 00:00:00
abstract::In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.02.008
更新日期:2015-05-01 00:00:00
abstract::Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2017.03.005
更新日期:2017-06-01 00:00:00
abstract::Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.10.002
更新日期:2007-11-01 00:00:00
abstract::Recent molecular cloning studies have identified several genes encoding alpha and beta subunits of the nicotinic acetylcholine receptor. These genes have distinct, although overlapping, patterns of expression in the brain and peripheral ganglia. Multiple nicotinic receptors with distinct pharmacological and functional...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(91)90486-c
更新日期:1991-01-01 00:00:00
abstract::Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.05.001
更新日期:2017-08-01 00:00:00
abstract::The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5-HT receptor subtype. The strong functional union of this family is reflected ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)88991-9
更新日期:1995-03-01 00:00:00
abstract::Apoptosis is an area of intense scientific interest, which encompasses the study of and triggers mechanisms involved in mediating the cell biology of programmed cell death. A number of low molecular weight compounds have been used to inhibit or enhance this fundamental cellular process and so apoptosis has now become ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01277-2
更新日期:1999-01-01 00:00:00
abstract::Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(92)90141-r
更新日期:1992-12-01 00:00:00
abstract::Insect nicotinic acetylcholine (nACh) receptors are molecular targets of insecticides such as neonicotinoids that are used to control disease-carrying insects and agricultural pests. To date, several insect nACh receptor subunits have been identified, indicating different nACh receptor subtypes and pharmacological pro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.11.006
更新日期:2007-01-01 00:00:00
abstract::The GPR119 receptor is expressed predominantly in pancreatic β cells and in enteroendocrine cells. It is a major target for the development of anti-diabetic drugs that through GPR119 activation may stimulate both insulin and GLP-1 release. GPR119 can be activated by oleoylethanolamide and several other endogenous lipi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2012.03.014
更新日期:2012-07-01 00:00:00