Abstract:
:There is much evidence suggesting that there is a strong relationship between the deterioration of brain lipid homeostasis, vascular changes and the pathogenesis of Alzheimer's disease (AD). These associations include: (1). recognition that a key cholesterol transporter, apolipoprotein E type 4, acts a major genetic risk factor for both familial and sporadic AD; (2). epidemiological studies linking cardiovascular risk factors, such as hypertension and high plasma cholesterol, to dementia; (3). the discovery that small strokes can precipitate clinical dementia in cognitively normal elderly subjects; (4). the modulation of degradation of the amyloid precursor protein by cholesterol administration in cell culture and in animal models of beta-amyloid overproduction; and (5). the beneficial effect of cholesterol-lowering drugs, such as Probucol and statins, in combating common AD. The recent finding that there is a genetic association between the HMGR gene locus and sporadic AD further suggests that brain cholesterol metabolism is central to AD pathophysiology, and a potential therapeutic target for disease stabilization and primary disease prevention.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Poirier Jdoi
10.1016/s1471-4914(03)00007-8keywords:
subject
Has Abstractpub_date
2003-03-01 00:00:00pages
94-101issue
3eissn
1471-4914issn
1471-499Xpii
S1471491403000078journal_volume
9pub_type
杂志文章,评审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
doi:10.1016/j.molmed.2019.05.004
更新日期:2019-08-01 00:00:00
abstract::Cardiovascular diseases predominantly result from atherosclerosis, a natural biological phenomenon reflecting food intake and energy production in humans. Lipolysis of plasma triglyceride-rich lipoproteins (TGRLs) by lipoprotein lipase (LPL) is an essential element of energy production that delivers free fatty acids t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2020.07.005
更新日期:2020-12-01 00:00:00
abstract::Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arte...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.07.001
更新日期:2017-09-01 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::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::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::In STEM, and particularly in science, many early career researchers find themselves isolated and lacking guidance. There is an enormous need to connect early career scientists with experienced professionals outside their immediate work environment. A new initiative aims to create a supportive community to foster commu...
journal_title:Trends in molecular medicine
pub_type: 社论
doi:10.1016/j.molmed.2019.08.007
更新日期:2019-11-01 00:00:00
abstract::miRNAs are small noncoding RNAs known to post-transcriptionally regulate gene expression. miRNAs are expressed in the heart where they regulate multiple pathophysiological processes. The discovery of stable cardiac miRNAs in the bloodstream has also motivated the investigation of their potential as biomarkers. This re...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.10.006
更新日期:2014-12-01 00:00:00
abstract::Many infectious agents elicit a type I interferon response but, until recently, the molecular details that coordinate interferon (IFN)-alpha and -beta expression during infection were unknown. Innate immune pattern recognition receptors, including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.07.006
更新日期:2005-09-01 00:00:00
abstract::The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor dise...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.10.009
更新日期:2015-01-01 00:00:00
abstract::Small intestine bacterial overgrowth (SIBO) occurs when colonic quantities of commensal bacteria are present in the small bowel. SIBO is associated with conditions of disrupted gastrointestinal (GI) motility leading to stasis of luminal contents. Recent data show that SIBO is also found in children living in unsanitar...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.11.001
更新日期:2015-01-01 00:00:00
abstract::Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-Eph...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.01.009
更新日期:2019-04-01 00:00:00
abstract::Betulinic acid (BA) derivatives are low molecular weight organic compounds synthesized from a plant-derived natural product. Several BA derivatives are potent and highly selective inhibitors of HIV-1. Depending on the specific side-chain modification, these compounds function by inhibiting HIV fusion or, as recently d...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.11.001
更新日期:2005-01-01 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::Carcinoma of the gastrointestinal tract is the most common internal malignancy affecting men and women in Western countries. Chronic intestinal inflammation, especially of the colon, is also a Western disease and correlates with a significantly increased risk of developing cancer. This has suggested that the immune pr...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(01)02107-4
更新日期:2001-10-01 00:00:00
abstract::House dust mite (HDM) allergy is a frequent inflammatory disease found worldwide. Although allergen-specific CD4(+) Th2 cells orchestrate the HDM allergic response, notably through induction of IgE directed towards mite allergens, recent studies have demonstrated that innate immunity activation also plays a critical r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.05.014
更新日期:2011-10-01 00:00:00
abstract::During the past decade, successful gene therapies for immunodeficiencies were finally brought to the clinic. This was accomplished through new gene therapy vectors and improved procedures for genetic modification of autologous hematopoietic stem cells. For HIV, autologous hematopoietic stem cell (HSC) gene therapy wit...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.08.004
更新日期:2014-11-01 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::While the hippocampus has long been recognized as a brain structure specialized in mapping 'space' in rodents, human studies and now recent data from rodents have shown that its function extends well beyond spatial coding. Recently, an overlooked area of the hippocampus, CA2, has emerged as a critical region for socia...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.06.007
更新日期:2016-08-01 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::Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics availabl...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.08.002
更新日期:2017-10-01 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 surfaces of all vertebrate cells are decorated with a dense and complex array of sugar chains, which are mostly attached to proteins and lipids. Most soluble secreted proteins are also similarly decorated with such glycans. Sialic acids are a diverse family of sugar units with a nine-carbon backbone that are typic...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.06.002
更新日期:2008-08-01 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::Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, intermediate traits such as gene expressi...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.10.004
更新日期:2020-02-01 00:00:00
abstract::Despite significant advances in the management of trauma victims, traumatic injury with the ensuing sepsis and multiple organ failure remains the leading cause of death between the ages of 18 and 44 in the USA. Recently, interest in the clinically and experimentally observed gender dimorphic response to traumatic inju...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(01)01917-7
更新日期:2001-02-01 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::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::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::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