Abstract:
:What biological factors account for resilience to pain or to behavioral stress? Here, we discuss examples of cellular and molecular mechanisms within disparate parts of the nervous system as contributors to such resilience. In some especially well-studied humans, it is possible to identify particular neuronal cell types in the peripheral nervous system (PNS) and pinpoint specific genes that are major contributors to pain resilience. We also discuss more complex factors that operate within the central nervous system (CNS) to confer resilience to behavioral stress. We propose that genetic and neurobiological substrates for resilience are discoverable and suggest more generally that neurology and psychiatry hold lessons for each other as investigators search for actionable, biological underpinnings of disease.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Nestler EJ,Waxman SGdoi
10.1016/j.molmed.2020.03.007subject
Has Abstractpub_date
2020-10-01 00:00:00pages
924-935issue
10eissn
1471-4914issn
1471-499Xpii
S1471-4914(20)30084-8journal_volume
26pub_type
杂志文章,评审abstract::Clustered regularly interspaced short palindromic repeats, or CRISPR, has been widely accepted as a versatile genome editing tool with significant potential for medical application. Reliable allele specificity is one of the most critical elements for successful application of this technology to develop high-precision ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.09.008
更新日期:2020-03-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin-1 and polycystin-2, respectively. Optimizing the folding environment for polycystin-1 missense mutations may have a critical effect on the progression of ADPKD in animal models and could potentially lead t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2016.10.001
更新日期:2016-12-01 00:00:00
abstract::Long-standing difficulties in the in vitro transformation of human cells have been overcome. Using telomerase, several successful oncogene-mediated transformations of human cells have been reported and the following cellular requirements for human cell transformation have been proposed: the maintenance of telomere seq...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.09.001
更新日期:2004-11-01 00:00:00
abstract::Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.01.005
更新日期:2016-03-01 00:00:00
abstract::The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors and is often associated with the acquisition of an aggressive phenotype. The Met oncogene, encoding the RTK for hepatocyte growth factor (HGF), controls genetic programs leading to cell growth, invasion and protection from apoptosis. The ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.04.005
更新日期:2005-06-01 00:00:00
abstract::Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imagin...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.08.006
更新日期:2010-12-01 00:00:00
abstract::The systemic inflammatory response is biologically complex, redundant, and activated by both infectious and noninfectious triggers. Its manipulation can cause both benefit and harm. More than 100 randomized clinical trials have tested the hypothesis that modulating the septic response to infection can improve survival...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.01.007
更新日期:2014-04-01 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::Physicians have, for over a century, attempted to harness the potential therapeutic power of the immune system to treat patients with cancer. The discovery that cancer regression can be achieved by immune rejection of tumour antigens theoretically allows the eradication of neoplastic cells without toxicity to normal t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.02.006
更新日期:2004-04-01 00:00:00
abstract::This review highlights recent advances in how the innate and adaptive immune systems control the blood-brain barrier (BBB) and the blood-nerve barrier (BNB). Interferons and TAM receptors play key roles in innate immune control of the BBB. Cells of the adaptive immune system, particularly CD4+ T cells, take distinct r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.01.004
更新日期:2017-03-01 00:00:00
abstract::The past few years have seen the identification of PTPN22 and the confirmation of CTLA-4 as common autoimmune disease genes. Together with MHC and INS, these developments have increased the collection of confirmed susceptibility loci for autoimmunity. In this article, the latest developments related to these genes and...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.12.005
更新日期:2006-02-01 00:00:00
abstract::Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(00)01910-9
更新日期:2001-03-01 00:00:00
abstract::Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive defic...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.03.003
更新日期:2015-06-01 00:00:00
abstract::In a recent paper by Dvela-Levitt et al., chemical screening using an immunofluorescent assay identified a compound that caused removal of a dominant-inherited misfolded secretory protein, mucin1-frameshifted, from an intracellular location in immortalized renal epithelial cells of a patient affected with progressive ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2019.08.011
更新日期:2019-10-01 00:00:00
abstract::Therapy for hepatitis C virus (HCV) infection is on the cusp of a new era. Until now, standard-of-care therapy has involved interferon (IFN) and ribavirin. With the first successful Phase III trials of specific targeted antiviral therapy for HCV (STAT-C) compounds, as well as three trials in progress giving the first ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.10.005
更新日期:2011-01-01 00:00:00
abstract::The social amoeba Dictyostelium discoideum is increasingly being used as a simple model for the investigation of problems that are relevant to human health. This article focuses on several recent examples of Dictyostelium-based biomedical research, including the analysis of immune-cell disease and chemotaxis, centroso...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2006.07.003
更新日期:2006-09-01 00:00:00
abstract::It is now well recognized that cells traffic in both directions between fetus and mother during pregnancy. Moreover, fetal cells have been found to persist for years, probably for a lifetime, in the circulation of healthy women. Harboring of cells from another individual at low levels is called microchimerism. Women h...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/s1471-4914(01)02269-9
更新日期:2002-03-01 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::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::A recent study introduced the existence of an 'immune clock' in pregnancy; during the course of gestation, peripheral blood cells from pregnant women were analyzed by mass cytometry using a single-cell signaling-based elastic net algorithm. The insights will undoubtedly promote the testing of such a clock - possibly i...
journal_title:Trends in molecular medicine
pub_type: 评论,杂志文章
doi:10.1016/j.molmed.2017.11.007
更新日期:2018-01-01 00:00:00
abstract::The p53 tumor suppressor protein has well-established roles in monitoring various types of stress signals by activating specific transcriptional targets that control cell cycle arrest and apoptosis, although some activities are also mediated in a transcription-independent manner. Here, we review the recent advances in...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.09.002
更新日期:2010-11-01 00:00:00
abstract::The Hedgehog (Hh) cascade controls cell proliferation, differentiation and patterning of tissues during embryogenesis but is largely suppressed in the adult. The Hh pathway can become reactivated in cancer. Here, we assimilate data from recent studies to understand how and when the Hh pathway is turned on to aid the n...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.05.003
更新日期:2010-08-01 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::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::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::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
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::In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.09.005
更新日期:2015-11-01 00:00:00
abstract::It is now widely accepted that the classic environmental risk factors for atherosclerosis only partly explain the incidence of coronary artery disease and the development of acute coronary syndromes. Therefore, genetic factors that vary among human populations seem to be involved in the clinical manifestations of such...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.08.004
更新日期:2008-10-01 00:00:00
abstract::Theoretical, desirable features of second-generation metal-on-metal (MoM) hip prostheses have led to their widespread use. However, the bearing surfaces, consisting of complex cobalt-chromium alloys, are subject to wear and the release of cobalt and chromium (CoCr) nanoparticles. These nanoparticles can reduce cellula...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.12.002
更新日期:2012-03-01 00:00:00