Abstract：
:Ten percent of inherited diseases are caused by premature termination codon (PTC) mutations that lead to degradation of the mRNA template and to the production of a non-functional, truncated polypeptide. In addition, many acquired mutations in cancer introduce similar PTCs. In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC. Since, many studies have validated this approach, but despite the promise of PTC readthrough therapies, the mechanisms of translation termination remain to be precisely elucidated before even more progress can be made. Here, we review the molecular basis for PTC readthrough in eukaryotes and describe currently available compounds with significant therapeutic potential for treating genetic disorders and cancer.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Bidou L,Allamand V,Rousset JP,Namy Odoi
10.1016/j.molmed.2012.09.008subject
Has Abstractpub_date
2012-11-01 00:00:00pages
679-88issue
11eissn
1471-4914issn
1471-499Xpii
S1471-4914(12)00185-2journal_volume
18pub_type
杂志文章,评审abstract：:Genetically engineered mouse models have revolutionized the study of pancreatic cancer, but have several technical and practical limitations. A new adeno-associated virus (AAV)-driven somatic genome-editing model of pancreatic ductal adenocarcinoma reported by Ideno et al. (Lab. Invest. published online February 6, 20...
journal_title：Trends in molecular medicine
pub_type： 信件
doi：10.1016/j.molmed.2019.02.012
更新日期：2019-05-01 00:00:00
abstract：:Pyocyanin (PCN) is a blue redox-active secondary metabolite that is produced by Pseudomonas aeruginosa. PCN is readily recovered in large quantities in sputum from patients with cystic fibrosis who are infected by P. aeruginosa. Despite in vitro studies demonstrating that PCN interferes with multiple cellular function...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2004.10.002
更新日期：2004-12-01 00:00:00
abstract：:Inflammatory signaling underlies many diseases, from arthritis to cancer. Our understanding of inflammation has thus far been limited to the world of proteins, because we are only just beginning to understand the role that noncoding RNAs (ncRNA) might play. It is now clear that ncRNA do not constitute transcriptional ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2017.11.003
更新日期：2018-01-01 00:00:00
abstract：:Since the discovery that IgE antibodies mediate allergy, decades of research have unraveled complex mechanisms associated with conventional immunotherapy and the vital protagonists that shape 'immune tolerance' to allergens. Debate exists on what should constitute the dominant effector mechanism in driving rational dr...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2020.01.007
更新日期：2020-04-01 00:00:00
abstract：:Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations fo...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2018.02.001
更新日期：2018-04-01 00:00:00
abstract：:The majority of biomedical and biological research relies on a few molecular biology techniques. Here we show that eight key molecular biology techniques would not exist without basic biological research. We also find that the scientific reward system does not sufficiently value basic biological research into molecula...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2018.12.003
更新日期：2019-02-01 00:00:00
abstract：:Genetic causes are thought to underlie about half of infertility cases, but understanding the genetic bases has been a major challenge. Modern genomics tools allow more sophisticated exploration of genetic causes of infertility through population, family-based, and individual studies. Nevertheless, potential therapies...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2020.12.008
更新日期：2021-01-08 00:00:00
abstract：:The inflammasome is a key regulator of immune responses in the gut. Two recent studies in the journal Cell demonstrate that epithelial inflammasome activation and IL-18 secretion can control intestinal homeostasis or induce autoinflammation. ILC3 cells are triggered to secrete IL-22, regulating IL-18 expression in epi...
journal_title：Trends in molecular medicine
pub_type： 评论,杂志文章
doi：10.1016/j.molmed.2016.02.008
更新日期：2016-04-01 00:00:00
abstract：:The mammalian target of rapamycin (mTOR), the key component of the protein complexes mTORC1 and mTORC2, plays a critical role in cellular development, tissue regeneration, and repair. mTOR signaling can govern not only stem cell development and quiescence but also cell death during apoptosis or autophagy. Recent studi...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2012.11.001
更新日期：2013-01-01 00:00:00
abstract：:Since the discovery of HIV over three decades ago, major efforts have been made to control and perhaps eliminate HIV infection worldwide. During these studies, certain myths or misconceptions about this infectious disease have been emphasized and other potentially beneficial concepts have received less attention. A tr...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2015.03.004
更新日期：2015-06-01 00:00:00
abstract：:H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel pe...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2005.10.006
更新日期：2005-12-01 00:00:00
abstract：:While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, a...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2019.10.001
更新日期：2020-02-01 00:00:00
abstract：:During fertilization, the spermatozoon penetrates through the cumulus cells and the zona pellucida that surrounds the oocyte, before it binds and fuses with the oocyte plasma membrane to induce activation. In vitro fertilization (IVF) studies performed in non-human mammals have contributed extensive knowledge regardin...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(01)01957-8
更新日期：2001-04-01 00:00:00
abstract：:Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs), which consist of an NSAID with an NO-donating moiety covalently attached to it, promise to contribute significantly towards the development of effective chemoprevention strategies against cancer. NO-NSAIDs inhibit the growth of cultured cancer cel...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2004.05.004
更新日期：2004-07-01 00:00:00
abstract：:Ten percent of the population worldwide suffers from chronic kidney disease (CKD), characterized by fibrotic changes in the kidney. Fibrosis is associated with loss of epithelial parenchyma, and accumulation of myofibroblasts, fibrillary collagen, and inflammatory cells. Two recent papers highlight the critical role o...
journal_title：Trends in molecular medicine
pub_type： 评论,杂志文章
doi：10.1016/j.molmed.2015.11.009
更新日期：2016-01-01 00:00:00
abstract：:Recently revised diagnostic guidelines for Alzheimer's disease (AD) emphasise the use of biomarkers, heralding a paradigm shift towards a more biological definition of the disorder. Currently available biomarkers offer added diagnostic accuracy in certain situations, but their performance in terms of early diagnostic ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2013.10.001
更新日期：2014-01-01 00:00:00
abstract：:Hundreds of millions of people worldwide are affected by bone-related diseases, such as osteoporosis and rheumatoid arthritis. Understanding the molecular mechanisms of bone metabolism is crucial for developing novel drugs for treating such diseases. In particular, genetic experiments showing that the receptor activat...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2005.11.007
更新日期：2006-01-01 00:00:00
abstract：:Successful molecular targeting of nanoparticle drug carriers can enhance therapeutic specificity and reduce systemic toxicity. Typically, ligands specific for cognate receptors expressed on the intended target cell type are conjugated to the nanoparticle surface. This approach, often called active targeting, seems to ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2018.05.003
更新日期：2018-07-01 00:00:00
abstract：:Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular and genetic data suggest that: (i) antipsychotic-naïve samples provide the g...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2010.10.010
更新日期：2011-02-01 00:00:00
abstract：:BAX is a formidable BCL-2 family protein that executes cellular suicide in response to physiologic and pathologic stress. A new article in Nature Chemical Biology (Garner et al.https://doi.org/10.1038/s41589-018-0223-0) reports small molecules that inhibit the conformational activation of BAX, informing a pharmacologi...
journal_title：Trends in molecular medicine
pub_type： 信件
doi：10.1016/j.molmed.2019.02.008
更新日期：2019-04-01 00:00:00
abstract：:The identification of functionally relevant polymorphisms of peptidylarginine deiminase 4, an enzyme that catalyzes the post-translational citrullination of proteins, as a rheumatoid arthritis gene is one of the most convincing success stories of complex disease gene mapping to date. In addition to an extensive single...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2003.08.007
更新日期：2003-10-01 00:00:00
abstract：:In the coming years, molecular diagnostics will continue to be of critical importance to public health worldwide. It will facilitate the detection and characterization of disease, as well as monitoring of the drug response, and will assist in the identification of genetic modifiers and disease susceptibility. A wide r...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/s1471-4914(02)02331-6
更新日期：2002-06-01 00:00:00
abstract：:Genome sequencing has the potential for stratified cancer treatment and improved diagnostics for rare disorders. However, sequencing needs to be utilised in risk stratification on a population scale to deepen the impact on the health system by addressing common diseases, where individual genomic variants have variable...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.04.001
更新日期：2014-09-01 00:00:00
abstract：:The protein network protecting the stability of the genome is defective in Fanconi anemia (FA). The newest in a series of FA proteins is involved in DNA damage response, but the mechanism is still unclear. Clues may come from yeast two-hybrid experiments, an extraordinarily successful tool for determining molecular fu...
journal_title：Trends in molecular medicine
pub_type： 新闻
doi：10.1016/s1471-4914(01)02042-1
更新日期：2001-06-01 00:00:00
abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal monogenic disorder, with more than 12 million cases worldwide. The two causative genes for ADPKD, PKD1 and PKD2, encode protein products polycystin-1 (PC1) and polycystin-2 (PC2 or TRPP2), respectively. Recent data have shed lig...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.01.004
更新日期：2014-05-01 00:00:00
abstract：:Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic m...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2006.11.005
更新日期：2007-01-01 00:00:00
abstract：:The emergence of Zika virus (ZIKV) infections in Latin America and Southeast Asia has created an urgent need for new, simple, yet sensitive, diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect ZIKV RNA as a new approach to achieve rapid development and deployment of ...
journal_title：Trends in molecular medicine
pub_type： 评论,杂志文章
doi：10.1016/j.molmed.2016.05.009
更新日期：2016-07-01 00:00:00
abstract：:Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RN...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(03)00032-7
更新日期：2003-04-01 00:00:00
abstract：:DNA vaccination is currently being explored as a potential strategy for combatting cancer. However, tumor antigens are often weak and the immune system of patients may be compromised. For B-cell tumors, immunoglobulin idiotypic antigens provide defined targets but are poorly immunogenic. Fusion of a sequence derived f...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/s1471-4914(01)02126-8
更新日期：2001-12-01 00:00:00
abstract：:Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumo...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/s1471-4914(02)02276-1
更新日期：2002-02-01 00:00:00
