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 role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons. GPR37 also constitutes a core structure of Lewy bodies, demonstrating a more general involvement in PD pathology. However, if folded and matured properly, GPR37 seems to be neuroprotective. Moreover, GPR37 modulates functionality of the dopamine transporter and the dopamine D2 receptor and stimulates dopamine neurotransmission. Here we review the multiple roles of GPR37 with relevance to potential disease modification and symptomatic therapies of PD and highlight unsolved issues in this field.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Leinartaité L,Svenningsson Pdoi
10.1016/j.tips.2017.05.006subject
Has Abstractpub_date
2017-08-01 00:00:00pages
749-760issue
8eissn
0165-6147issn
1873-3735pii
S0165-6147(17)30114-1journal_volume
38pub_type
杂志文章,评审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::From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2010.08.006
更新日期:2010-12-01 00:00:00
abstract::Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(94)90322-0
更新日期:1994-07-01 00:00:00
abstract::It is generally accepted that muscle wasting is caused by an increase in protein breakdown which seems to be associated with an ATP-dependent, non-lysosomal proteolytic system based on conjugation of proteins to the small polypeptide ubiquitin. Increases in ubiquitin conjugates and in ubiquitin mRNAs are found in the ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(96)10021-3
更新日期:1996-06-01 00:00:00
abstract::Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01261-9
更新日期:1998-11-01 00:00:00
abstract::Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.09.004
更新日期:2013-11-01 00:00:00
abstract::Ischaemia-reperfusion (I/R) injury is a common feature of several diseases associated with high morbidity and mortality, such as stroke and myocardial infarction. The damaged tissue displays cardinal signs of inflammation and microvascular injury that, unless resolved, lead to long-term tissue damage with associated d...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.04.001
更新日期:2010-06-01 00:00:00
abstract::Annexin A1 (ANXA1) is an endogenous protein known to have potent anti-inflammatory properties in the peripheral system. It has also been detected in the brain, but its function there is still ambiguous. In this review, we have, for the first time, collated the evidence currently available on the function of ANXA1 in t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.12.003
更新日期:2008-03-01 00:00:00
abstract::Receptors, enzymes, and ion channels are traditional targets of therapeutic development. A common strategy is to target these proteins with agents that either activate or suppress their activity with ligands or substrates that occupy orthosteric sites or have allosteric interactions. An alternative approach involves r...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.05.004
更新日期:2015-08-01 00:00:00
abstract::Exposing the heart to brief episodes of ischaemia protects the myocardium and vascular endothelial cells against functional damage and cell death caused by subsequent prolonged ischaemia. Elucidation of the mechanisms that are involved in this phenomenon known as 'ischaemic preconditioning' and identification of drugs...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01483-8
更新日期:2000-06-01 00:00:00
abstract::Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01268-1
更新日期:1998-12-01 00:00:00
abstract::The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2003.11.005
更新日期:2004-01-01 00:00:00
abstract::Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.08.001
更新日期:2016-11-01 00:00:00
abstract::The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01097-3
更新日期:1997-09-01 00:00:00
abstract::G-protein-coupled receptors (GPCRs) are dynamically regulated by various mechanisms that tune their response to external stimuli. Modulation of their plasma membrane density, via trafficking between subcellular compartments, constitutes an important process in this context. Substantial information has been accumulated...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2008.07.009
更新日期:2008-10-01 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::NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a diverse group of neurological disorders associated with excessive activation of excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in the development of therapeutically useful NMDA receptor channel blockers an...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(93)90005-5
更新日期:1993-09-01 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::In the discipline of pharmacology, drugs (ligands) are used as tools to elucidate the processes of biological systems. Because of this, pharmacologists strive to delineate all characteristics of drugs. Decades of research have resulted in the proposal that ligands possess two properties that are intrinsic to the ligan...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01138-3
更新日期:1998-07-01 00:00:00
abstract::This year marks the 90th anniversary of the publication of Hans Horst Meyer's classic paper in which he proposed that the ability of a substance to produce narcosis or anesthesia is governed by its partition coefficient. In this article, Robert Lipnick describes the experiments carried out by Meyer and his colleagues ...
journal_title:Trends in pharmacological sciences
pub_type: 传,历史文章,杂志文章
doi:10.1016/0165-6147(89)90025-4
更新日期:1989-07-01 00:00:00
abstract::The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and ...
journal_title:Trends in pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1016/j.tips.2006.01.001
更新日期:2006-03-01 00:00:00
abstract::Pharmacology training in Canada was initiated at McGill University in Montréal in 1824, and there are now 17 pharmacology departments in Canada offering graduate training to more than 500 students. In this article, Gerald Marks reviews the growth of pharmacology in Canada since the early 19th century in both academic ...
journal_title:Trends in pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1016/0165-6147(94)90312-3
更新日期:1994-07-01 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::The GABAA receptor belongs, along with the nicotinic acetylcholine receptor, the glycine receptor and the 5-HT3 receptor, to a family of homologous transmitter-gated ion channels mediating fast synaptic transmission. Many classes of drug interact with the GABAA receptor, which is the major inhibitory ion channel in th...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01118-8
更新日期:1997-11-01 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::Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered for treatment and prevention of Alzheimer's disease (AD) for more than two decades. Biochemical markers in the brains of individuals with AD suggest that inflammation might be a driving cause of the disease that can be suppressed by drug treatment. In...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.09.004
更新日期:2007-10-01 00:00:00
abstract::Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain barrier, and the irreplaceable nature of neurons. Here, we revie...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.04.013
更新日期:2019-07-01 00:00:00
abstract::Hormesis is a generalizable dose-response relationship characterized by low-dose stimulation and high-dose inhibition. Despite debate over this biphasic dose-response curve, hormesis is challenging central beliefs in the evaluation of chemicals or drugs and has influenced biological model selection, concentration rang...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2020.05.004
更新日期:2020-08-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is caused mostly by cigarette smoking but its specific molecular mechanisms are obscure. Current theories suggest that the inflammation and oxidative stress induced by smoking lead to proteolytic imbalance and progressive lung structural derangement, with disease susceptibi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(02)00052-4
更新日期:2003-02-01 00:00:00
abstract::Recently, nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown, using different techniques, to mobilize intracellular Ca2+ stores in invertebrate, lower vertebrate, plant and mammalian cells. This endogenous molecule might play an atypical role in Ca2+ signalling by coordinating the responses of other ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01990-8
更新日期:2002-04-01 00:00:00