Abstract：
:Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cases, the identification and specific removal of 'dispensable' exons by exon-skipping ASOs could potentially bypass lethal mutations in other genes and bring clinical benefits to affected individuals carrying amenable mutations. In this review, we discuss the potential of therapeutic alternative splicing, with a particular focus on targeted exon skipping using Duchenne MD as an example, and speculate on new applications for other inherited rare diseases where redundant or dispensable exons may be amenable to exon-skipping ASO intervention as precision medicine.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Li D,Mastaglia FL,Fletcher S,Wilton SDdoi
10.1016/j.tips.2018.09.001subject
Has Abstractpub_date
2018-11-01 00:00:00pages
982-994issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(18)30145-7journal_volume
39pub_type
杂志文章,评审abstract：:The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01201-2
更新日期：1998-05-01 00:00:00
abstract：:Ubiquitination is a highly conserved post-translational modification that regulates protein trafficking, function, and turnover. Ubiquitin ligases (E3s) conjugate ubiquitin polypeptides on substrates, whereas deubiquitnases (DUBs) reverse ubiquitination. Engineering of chemical antagonists and inhibitors of ubiquitin ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.01.005
更新日期：2014-04-01 00:00:00
abstract：:Pharmacological studies as well as molecular cloning of 5-HT receptors have revealed a multiplicity of receptor subtypes, not only in mammals but, as discussed in this review by René Hen, also in molluscs and arthropods. Most of these receptors belong to the G protein-coupled receptor family, and their mechanism of ac...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(92)90054-a
更新日期：1992-04-01 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：: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：:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/s0165-6147(99)01428-5
更新日期：2000-02-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.06.002
更新日期：2006-08-01 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
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01105-x
更新日期：1997-10-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.05.010
更新日期：2016-09-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.10.002
更新日期：2011-01-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02062-x
更新日期：2002-08-01 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：: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-k...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.09.007
更新日期：2006-11-01 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：:B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.09.008
更新日期：2019-11-01 00:00:00
abstract：:The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G protein-coupled receptors (GPCRs) as potential drug targets. The impact on human health has been trem...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.05.009
更新日期：2015-09-01 00:00:00
abstract：:5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain mon...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2007.01.002
更新日期：2007-03-01 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
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.04.010
更新日期：2015-06-01 00:00:00
abstract：:The alpha-adrenoceptor was subdivided into three subtypes: alpha 2A-, alpha 2B- and alpha 2C-adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of ge...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01063-8
更新日期：1997-06-01 00:00:00
abstract：:Fatty acid amide hydrolase (FAAH) is a hydrolytic enzyme that recognizes as substrates and inactivates the two most studied endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG). Following the observation that endocannabinoids produced by tissues during pathological conditions often have protective roles, FAA...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2008.03.001
更新日期：2008-05-01 00:00:00
abstract：:Nuclear receptors represent a large class of ligand-activated transcriptional regulators; about 70 members of this protein family have been cloned from mammalian or insect species. Thus, it came as a great surprise when the recent completion of the Caenorhabditis elegans genome revealed at least 228 genes for nuclear ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01417-0
更新日期：2000-03-01 00:00:00
abstract：:Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biol...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2010.07.002
更新日期：2010-10-01 00:00:00
abstract：:Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.06.001
更新日期：2005-08-01 00:00:00
abstract：:Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
journal_title：Trends in pharmacological sciences
pub_type： 评论,信件
doi：10.1016/j.tips.2016.06.001
更新日期：2016-08-01 00:00:00
abstract：:The metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2019.02.006
更新日期：2019-04-01 00:00:00
abstract：:Stem cells derived from pre-implantation human embryos or from somatic cells by reprogramming are pluripotent and self-renew indefinitely in culture. Pluripotent stem cells are unique in being able to differentiate to any cell type of the human body. Differentiation towards the cardiac lineage has attracted significan...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2009.07.001
更新日期：2009-10-01 00:00:00
abstract：:Classical targeted drug discovery is based on targeting druggable targets, typically kinases and receptors of which the function can be agonized or antagonized. This strategy meets difficulties in cases such as Huntington's disease (HD) and similar neurodegenerative disorders, where the pathological function of the pr...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.12.001
更新日期：2014-02-01 00:00:00
abstract：:Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)01720-x
更新日期：2001-06-01 00:00:00
