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 light on the role of PC1 in regulating the severity of the cystic phenotypes in ADPKD, autosomal recessive polycystic kidney disease (ARPKD), and isolated autosomal dominant polycystic liver disease (ADPLD). These studies showed that the rate for cyst growth was a regulated trait, a process that can be either sped up or slowed down by alterations in functional PC1. These findings redefine the previous understanding that cyst formation occurs as an 'on-off' process. Here, we review these and other related studies with an emphasis on their translational implications for polycystic diseases.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Fedeles SV,Gallagher AR,Somlo Sdoi
10.1016/j.molmed.2014.01.004subject
Has Abstractpub_date
2014-05-01 00:00:00pages
251-60issue
5eissn
1471-4914issn
1471-499Xpii
S1471-4914(14)00005-7journal_volume
20pub_type
杂志文章,评审abstract::T-cell-mediated autoimmunity participates in physiological defense, maintenance and repair of the adult brain. However, unless such autoimmune responses to insults are rigorously controlled, they might lead to an autoimmune disease or other immune-related defects, where destructive activity outweighs the beneficial ef...
journal_title:Trends in molecular medicine
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doi:10.1016/j.molmed.2006.01.003
更新日期:2006-03-01 00:00:00
abstract::Protein S-nitrosylation constitutes a large part of the ubiquitous influence of nitric oxide on cellular signal transduction and accumulating evidence indicates important roles for S-nitrosylation both in normal physiology and in a broad spectrum of human diseases. Here we review recent findings that implicate S-nitro...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.06.007
更新日期:2009-09-01 00:00:00
abstract::Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-ka...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.09.002
更新日期:2007-11-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are currently being tested in clinical trials for the treatment of various diseases owing to the ease of generating and expanding these cells, the ability to differentiate them into various specialized mesenchymal tissue types and their immunosuppressive properties. However, their immunom...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.10.004
更新日期:2012-02-01 00:00:00
abstract::Induction of pathogen-specific binding antibodies has long been considered a signature of protective immunity following vaccination and infection. The humoral immune response is a complex network of antibodies that target different specificities and drive different functions, collectively acting to limit and clear inf...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.09.002
更新日期:2016-11-01 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::When diabetes is diagnosed, the majority of insulin-secreting pancreatic β cells are already dysfunctional or destroyed. This β cell dysfunction/destruction usually takes place over many years, making timely detection and clinical intervention difficult. For this reason, there is immense interest in developing tools t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
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更新日期:2019-08-01 00:00:00
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journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.05.002
更新日期:2008-07-01 00:00:00
abstract::For decades it has been assumed that T cells reject tumors essentially by direct killing. However, solid tumors are composed of malignant cells and a variety of different nonmalignant cells, referred to as tumor stroma. Stromal cells, such as endothelial cells, fibroblasts and inflammatory cells, often support tumor g...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.03.002
更新日期:2005-05-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) are cutting edge biotechnology that may revolutionize medicine, and creating iPSCs from ethnically diverse individuals would generate valuable therapeutic and drug development tools. However, challenges must be overcome in creating the infrastructure and scientific capacity neede...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2012.10.005
更新日期:2012-12-01 00:00:00
abstract::Accumulating evidence has revealed that immunogenic cell death triggered by particular chemotherapeutic agents plays a critical role in harnessing antitumor immunity to clinical responses. However, negative regulatory pathways exist which suppress the induction of effective immune responses by a broad spectrum of anti...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2013.06.001
更新日期:2013-09-01 00:00:00
abstract::The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortica...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.07.008
更新日期:2011-12-01 00:00:00
abstract::In a meticulous study, Humbert, Durr, and colleagues showed evidence for aberrant neurodevelopment in both Huntington's disease (HD) and mouse models of HD. We consider the implications of prenatal pathological changes for the onset and progression of HD and their relatedness to current therapeutic plans. ...
journal_title:Trends in molecular medicine
pub_type: 评论,杂志文章
doi:10.1016/j.molmed.2020.08.004
更新日期:2020-10-01 00:00:00
abstract::Epigenome-wide association studies (EWASs) provide a systematic approach to uncovering epigenetic variants underlying common diseases. Discoveries have shed light on novel molecular mechanisms of disease and enabled the application of epigenetic variants as biomarkers. Here, we highlight the recent advances in this em...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.07.002
更新日期:2014-10-01 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::Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evid...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.04.004
更新日期:2017-06-01 00:00:00
abstract::Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulator...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.07.001
更新日期:2016-09-01 00:00:00
abstract::Chronic hepatitis C is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although current treatment options are limited, progress in understanding the molecular virology of hepatitis C has led to the identification of novel antiviral targets. Moreover, in vitro and in vivo model systems have b...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(02)02395-x
更新日期:2002-10-01 00:00:00
abstract::Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2006.10.004
更新日期:2006-12-01 00:00:00
abstract::Imported across the plasma membrane by SLC1A5, glutamine has emerged as a metabolic fuel that is catabolized by mitochondrial glutaminase to support tumor growth. The missing link between cytoplasmic and mitochondrial glutamine metabolism is now provided by Yoo et al., identifying the mitochondrial glutamine importer ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2019.11.004
更新日期:2020-01-01 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::Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated p...
journal_title:Trends in molecular medicine
pub_type: 临床试验,杂志文章,评审
doi:10.1016/j.molmed.2011.01.011
更新日期:2011-06-01 00:00:00
abstract::Ubiquitin-containing cellular inclusions are characteristic of major neurodegenerative diseases and suggest an involvement of the ubiquitin-proteasome system. The frameshifted form of ubiquitin has proved to be a valuable tool for studying the role of the ubiquitin-proteasome system. It is an endogenous reporter for p...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.09.001
更新日期:2005-11-01 00:00:00
abstract::Sex differences have been clinically documented in numerous neurodegenerative diseases and yet the reasons for these differences are not well understood. Recent studies have found that microglia, the innate immune cells of the central nervous system, are a key cell type involved in neurodegenerative diseases. This cel...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.05.001
更新日期:2019-09-01 00:00:00
abstract::Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlate...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(02)02317-1
更新日期:2002-01-01 00:00:00
abstract::cAMP-dependent protein kinase A (PKA) signaling has a key role in memory processes and has been identified as a potential therapeutic target for memory disorders. The activation of PKA signaling is crucial for the consolidation of long-term memories dependent on the hippocampus and/or the amygdala, By contrast, initia...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.01.006
更新日期:2005-03-01 00:00:00
abstract::Here, we explore the potential of single-cell genomic analysis in blood for early detection of cancer; we consider a method that screens the presence of recurrent patterns of copy number (CN) alterations using sparse single-cell sequencing. We argue for feasibility, based on in silico analysis of existing single-cell ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.05.005
更新日期:2017-07-01 00:00:00
abstract::Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly under...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.05.005
更新日期:2007-07-01 00:00:00
abstract::Wound repair is a highly regulated process that requires the interaction of various cell types. It has been shown that cancers use the mechanisms of wound healing to promote their own growth. Therefore, it is of importance to identify common regulators of wound repair and tumor formation and to unravel their functions...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2020.07.009
更新日期:2020-12-01 00:00:00
abstract::Although significant progress has been made in understanding autoimmunity, no immunotherapy to effectively halt immune-mediated destruction of β cells in type 1 diabetes (T1D) is currently available. For successful immunotherapy it will be necessary to identify novel drug targets as well as robust immunologic biomarke...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2018.08.005
更新日期:2018-11-01 00:00:00