Abstract:
:Necrotic cell death has long been considered an accidental and uncontrolled mode of cell death. But recently it has become clear that necrosis is a molecularly regulated event that is associated with pathologies such as ischemia-reperfusion (IR) injury, neurodegeneration and pathogen infection. The serine/threonine kinase receptor-interacting protein 1 (RIP1) plays a crucial role during the initiation of necrosis induced by ligand-receptor interactions. On the other hand, ATP depletion is an initiating factor in ischemia-induced necrotic cell death. Common players in necrotic cell death irrespective of the stimulus are calcium and reactive oxygen species (ROS). During necrosis, elevated cytosolic calcium levels typically lead to mitochondrial calcium overload, bioenergetics effects, and activation of proteases and phospholipases. ROS initiates damage to lipids, proteins and DNA and consequently results in mitochondrial dysfunction, ion balance deregulation and loss of membrane integrity. Membrane destabilization during necrosis is also mediated by other factors, such as acid-sphingomyelinase (ASM), phospholipase A(2) (PLA(2)) and calpains. Furthermore, necrotic cells release immunomodulatory factors that lead to recognition and engulfment by phagocytes and the subsequent immunological response. The knowledge of the molecular mechanisms involved in necrosis has contributed to our under-standing of necrosis-associated pathologies. In this review we will focus on the intracellular and intercellular signaling events in necrosis induced by different stimuli, such as oxidative stress, cytokines and pathogen-associated molecular patterns (PAMPs), which can be linked to several pathologies such as stroke, cardiac failure, neurodegenerative diseases, and infections.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Vanlangenakker N,Vanden Berghe T,Krysko DV,Festjens N,Vandenabeele Pdoi
10.2174/156652408784221306subject
Has Abstractpub_date
2008-05-01 00:00:00pages
207-20issue
3eissn
1566-5240issn
1875-5666journal_volume
8pub_type
杂志文章,评审abstract:PURPOSE:To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patie...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524015666150731100012
更新日期:2015-01-01 00:00:00
abstract::By eliminating the unneeded or mutant cells, programmed cell death actively participates in a wide range of biological processes from embryonic development to homeostasis maintenance in adult. Continuing efforts have identified multiple cell death pathways, with apoptosis, necrosis and autophage the mostly studied. Re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666151026100339
更新日期:2015-01-01 00:00:00
abstract::Until recently it was believed that TNF-induced apoptosis is mediated exclusively by TNF-RI because TNF-RII lacks death domain. However, it has been demonstrated that TNF-RII enhances TNF-RI-mediated apoptosis. In this review, I have discussed the evidence and mechanisms by which TNF-RII regulates TNF-alpha-induced ap...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013363780
更新日期:2001-07-01 00:00:00
abstract::Hypoxia is a major hallmark of the tumor microenvironment that is strictly associated with rapid cancer progression and induction of metastasis. Hypoxia inhibits disulfide bond formation and impairs protein folding in the Endoplasmic Reticulum (ER). The stress in the ER induces the activation of Unfolded Protein Respo...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160523143937
更新日期:2016-01-01 00:00:00
abstract::A critical challenge faced by clinical nephrologists today is the escalating number of patients developing end stage renal disease, a major proportion of which is attributed to diabetic nephropathy (DN). The need for new measures to prevent and treat this disease cannot be overemphasized. To this end, modern genetic a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054553504
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Liver kinase B1 (LKB1)/5'-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer's disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190315164120
更新日期:2019-01-01 00:00:00
abstract::Mucolipidosis Type IV (MLIV) is a lysosomal storage disorder that is characterized by severe neurologic and ophthalmologic abnormalities. It is a progressive disease that usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones. First described in 1974, ML...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362276
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. METHODS:Whole-mount in situ hybridization and embryo immunostaining were performed. RESULTS:Zebrafish Fhl1A is the homologue of human F...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180308113909
更新日期:2017-01-01 00:00:00
abstract::The cell adhesion molecule integrin αvβ3 is an important player in the process of angiogenesis. In the last decades, a series of radiolabeled Arg-Gly-Asp (RGD) peptides targeting integrin αvβ3 has been prepared and optimized for positron emission tomography (PET) and single-photon-emission computed tomography (SPECT) ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131111115347
更新日期:2013-12-01 00:00:00
abstract::The leading cause of blindness in the developed world results from several disorders that have pathologic ocular neovascularization as the common pathway leading to vision loss. These disorders include exudative age related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), retina...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409789712783
更新日期:2009-11-01 00:00:00
abstract::Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick by hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents may also be used to alter splicing. Developing antisense technology involves the creation of a n...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043360375
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:To detect mutations of trypsinogen gene (PRSS1) in patients with autoimmune pancreatitis (AIP) and to determine the underlying pathogenesis. METHODS:DNA sequencing was used to detect full-length of PRSS1, cystic fibrosis transmembrane conductance regulator (CFTR), and pancreatic secretory trypsin inhibitor (...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524013666131118114432
更新日期:2014-03-01 00:00:00
abstract::Nanotechnology has witnessed tremendous advancement over the last several decades. Zinc oxide (ZnO), which can exhibit a wide variety of nanostructures, possesses unique semiconducting, optical, and piezoelectric properties hence has been investigated for a wide variety of applications. The most important features of ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131111130058
更新日期:2013-12-01 00:00:00
abstract::Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as ant...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411794474365
更新日期:2011-02-01 00:00:00
abstract::Many potential HIV vaccine strategies are being explored in both animal model and human settings. The success of any vaccine relies on relevant antigenic determinants being presented to the immune system for the activation of broad and long-lasting immunity. Effective immunity against HIV infection will likely require...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479870
更新日期:2003-05-01 00:00:00
abstract::Citrate is one of the major substrates for intracellular metabolism. The extracellular level of citrate is stable in blood but varies locally, with slightly increased levels in brain and high levels in prostate. Recent metabolomics research suggests that citrate level is a potential harbinger of different pathophysiol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666151123104855
更新日期:2015-01-01 00:00:00
abstract::Several species of kinetoplastid protozoa cause major human infectious diseases. Trypanosoma cruzi is responsible for the fatal Chagas disease in large parts of South America, the various species of Leishmania cause a number of different human diseases with millions of patients world-wide, and the African trypanosome ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043360113
更新日期:2004-09-01 00:00:00
abstract::Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783565595
更新日期:2008-02-01 00:00:00
abstract::Type 2 diabetes carries a 2-6-fold increased risk of cardiovascular disease (CVD) and death. Indeed, the risk of major cardiovascular events in Type 2 diabetic patients without history of coronary heart disease (CHD) is equivalent to that observed in non-diabetic subjects with CHD. However, atherosclerosis may also pr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053766095
更新日期:2005-05-01 00:00:00
abstract::Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The is...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406777435453
更新日期:2006-06-01 00:00:00
abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795677963
更新日期:2011-06-01 00:00:00
abstract::Autophagy is a bulk cytosolic degradative process which in the last few years has become a key pathway for the advancement of molecular medicine. Autophagy (cellular self-eating) has several implications in human disorders involving accumulation of cytosolic protein aggregates such as Alzheimer, Parkinson, Huntington ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783769634
更新日期:2008-03-01 00:00:00
abstract::In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are curr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652405774641052
更新日期:2005-11-01 00:00:00
abstract::As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those as...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479447
更新日期:2003-11-01 00:00:00
abstract::Pigment epithelium-derived factor (PEDF) is reported to play a protective role against diabetic vascular complications through its anti-oxidative properties. However, since a commercially available kit is not suitable for measurement of serum PEDF in humans, kinetics and regulation of serum PEDF are not known in these...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652410791065318
更新日期:2010-04-01 00:00:00
abstract::Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407780059159
更新日期:2007-03-01 00:00:00
abstract::The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compoun...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411797536688
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND:Inclusion of anticancer drugs into biocompatible nanoparticulate carriers decreases the general toxicity and improves the efficacy of clinical treatments due to the reduction of soluble circulating free drug. METHODS:In addition, removal of emerging drug contaminants from wastewaters is a necessity that sho...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524021666210111104428
更新日期:2021-01-10 00:00:00
abstract::Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cell...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409787314471
更新日期:2009-02-01 00:00:00
abstract::PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131118100542
更新日期:2014-01-01 00:00:00