Abstract：
:Nanomolar β-amyloid peptide (Aβ) can induce neuronal loss in culture by activating microglia to phagocytose neurons. We report here that this neuronal loss is mediated by the bridging protein lactadherin/milk-fat globule epidermal growth factor-like factor 8 (MFG-E8), which is released by Aβ-activated microglia, binds to co-cultured neurons and opsonizes neurons for phagocytosis by microglia. Aβ stimulated microglial phagocytosis, but did not opsonize neurons for phagocytosis. Aβ (250 nM) induced delayed neuronal loss in mixed glial-neuronal mouse cultures that required microglia and occurred without increasing neuronal apoptosis or necrosis. This neuronal death/loss was prevented by antibodies to MFG-E8 and was absent in cultures from Mfge8 knockout mice (leaving viable neurons), but was reconstituted by addition of recombinant MFG-E8. Thus, nanomolar Aβ caused neuronal death by inducing microglia to phagocytose otherwise viable neurons via MFG-E8. The direct neurotoxicity of micromolar Aβ was not affected by MFG-E8. The essential role of MFG-E8 in Aβ-induced phagoptosis, suggests this bridging protein as a potential therapeutic target to prevent neuronal loss in Alzheimer's disease.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Neniskyte U,Brown GCdoi
10.1111/jnc.12288subject
Has Abstractpub_date
2013-08-01 00:00:00pages
312-7issue
3eissn
0022-3042issn
1471-4159journal_volume
126pub_type
杂志文章abstract：:The biogenic amine serotonin (5-HT) plays a key role in the regulation and modulation of many physiological and behavioural processes in both vertebrates and invertebrates. These functions are mediated through the binding of serotonin to its receptors, of which 13 subtypes have been characterized in vertebrates. We ha...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04012.x
更新日期：2006-09-01 00:00:00
abstract：:A rat kidney epithelial cell line expressing the rat neurokinin-1 receptor (NK-1 R) was used to investigate the relationship between receptor phosphorylation and desensitization. Substance P (SP) maximally stimulated cellular inositol 1,4,5-trisphosphate (IP3) production 14-fold within 3 s, after which cellular IP3 le...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:In rats rendered hyperthyroid by chronic treatment with L-triiodothyronine (T3) hormone there was a 21 and 27% decrease, respectively, in the number of binding sites for [3H]flunitrazepam ([3H]FNZ) and [3H]ethyl-beta-carboline-3-carboxylate ([3H]beta-CCE) without changes in affinity for the two ligands. Two weeks afte...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb08767.x
更新日期：1985-05-01 00:00:00
abstract：:The cleavage-product of amyloid precursor protein (APP) constitutes the core component of plaques found in the brains of Alzheimer's disease (AD) patients. APP is ubiquitously expressed and its precise physiological functions remain unclear. This protein has been proposed to regulate synaptic function and processes un...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04672.x
更新日期：2007-09-01 00:00:00
abstract：:GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06419.x
更新日期：2009-12-01 00:00:00
abstract：:The adaptor protein Disabled1 (Dab1) interacts with amyloid precursor protein (APP) and decreases its pathological processing, an effect mediated by Fyn tyrosine kinase. Fyn is highly enriched in lipid rafts, a major site of pathological APP processing. To investigate the role of Fyn in the localization and phosphoryl...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07296.x
更新日期：2011-09-01 00:00:00
abstract：:Primary cultures of astrocytes from newborn rat brain showed evidence of a substrate-saturable process for glucose transport. The system shows a relatively high affinity for the substrate, with an apparent Km of approximately 1 mM. Maintenance of the cells in medium containing thyroid-hormone-free serum for 3, 6, or 9...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb07239.x
更新日期：1985-11-01 00:00:00
abstract：:Cytokines and catecholamines are known to constitute a significant portion of the regulatory neuroimmune networks involved in maintaining homeostasis in the central nervous system (CNS). Although we have already reported an increase in norepinephrine (NE) turnover within the locus coeruleus (LC) at 2 and 4 h after the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03209.x
更新日期：2005-07-01 00:00:00
abstract：:Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine-rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13612
更新日期：2016-06-01 00:00:00
abstract：:In developing CNS D1 dopamine receptor-imaging agents with improved specificity and longer brain retention, an iodinated D1 ligand was synthesized. In vitro and in vivo radiolabeling studies of a new iodinated benzazepine, TISCH [7-chloro-8-hydroxy-1-(3'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3- benzazepine], an a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09300.x
更新日期：1992-01-01 00:00:00
abstract：:Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C-terminus of the MJD-1 gene product, ataxin-3. Ataxin-3 is degraded by the proteasome. However, the precise mechanism of ataxin-3 degradation remains to be elucidated. In this st...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04460.x
更新日期：2007-06-01 00:00:00
abstract：:The recycling of methionine via homocysteine was measured in vivo in brain. After constant intravenous infusions (5 h) of both [3H-methyl]methionine and [35S]methionine into rats, the ratios of [3H-methyl]methionine to [35S]methionine in liver, brain, and plasma were determined. Similar experiments were performed in r...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb04631.x
更新日期：1980-01-01 00:00:00
abstract：:The roles of the intracellular calcium pool involved in regulating the Ca2+ profile and the neuronal survival rate during development were studied by using thapsigargin (TG), a specific inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase in cultured cerebellar granule neurons. Measuring the neuronal [Ca2+]i directly i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0730457.x
更新日期：1999-08-01 00:00:00
abstract：:Previously, we identified protein kinase FA/glycogen synthase kinase-3 (GSK-3) as a microtubule-associated protein tau kinase that can incorporate 4 mol of phosphates into 1 mol of tau protein and cause its electrophoretic mobility shift in sodium dodecyl sulfate gels, a unique property characteristic of paired helica...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb09811.x
更新日期：1993-11-01 00:00:00
abstract：:Choline acetyltransferase (ChAT) catalyzes the reaction between choline and acetylcoenzyme A (AcCoA) to form acetylcholine (ACh) in nerve terminals. ACh metabolism has implications in numerous aspects of physiology and varied disease states, such as Alzheimer's disease. Therefore a specific, sensitive, and reliable me...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2012.07793.x
更新日期：2012-08-01 00:00:00
abstract：:Hypoxic preconditioning (HP) 24 h before hypoxic-ischemic (HI) injury confers significant neuroprotection in neonatal rat brain. Recent studies have shown that the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) intracellular signaling pathways play a role in the induction of tolerance...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02324.x
更新日期：2004-04-01 00:00:00
abstract：:The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 mi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.740684.x
更新日期：2000-02-01 00:00:00
abstract：:In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attra...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00488.x
更新日期：2001-09-01 00:00:00
abstract：:beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) using biotin hydrazide and the coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated thr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb13015.x
更新日期：1986-02-01 00:00:00
abstract：:Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins that modulate neurotransmitter and G protein signaling. RGS7 and its binding partners Galpha and Gbeta5 are enriched in brain, but biochemical mechanisms governing RGS7/Galpha/Gbeta5 interactions and membrane association are poorly defined....
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752103.x
更新日期：2000-11-01 00:00:00
abstract：:35SO4-labeled fast-transported proteins of bullfrog dorsal root ganglion neurons were separated by two-dimensional gel electrophoresis, and their mobilities were compared to similar species labeled with [3H]mannose or [3H]fucose. Fluorography revealed regions of poorly resolved, high molecular weight material, likely ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb09055.x
更新日期：1983-10-01 00:00:00
abstract：:Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep inducer, and it is involved in the control of odor and pain responses and body temperature. In addition, PGD synthase transports lipophilic molecules in the subarachn...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750460.x
更新日期：2000-08-01 00:00:00
abstract：:In the last 40 years, especially with the application of new neurochemical and molecular biological techniques, there has been explosive progress in understanding how certain ligands and drugs are transported across the blood-brain barrier and choroid plexus out of brain and CSF. In the CNS, there are several separate...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2009.06451.x
更新日期：2010-01-01 00:00:00
abstract：:Intracellular calcium ions regulate the structure and functions of cytoskeletal proteins. On the other hand, recent studies have shown that the cytoskeleton, and actin filaments in particular, can modulate calcium influx through plasma membrane ligand- and voltage-gated channels. We now report that calcium release fro...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01059.x
更新日期：2002-08-01 00:00:00
abstract：:Dopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we appr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2006.04241.x
更新日期：2007-02-01 00:00:00
abstract：:The aim of the present study was to gain a deeper insight into the cell signaling pathways involved in the neuroprotection/neurorescue activity of the major green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG). EGCG (1 micro m) caused an immediate (30 min) down-regulation (approximately 40%) of Bad protein level...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04265.x
更新日期：2007-02-01 00:00:00
abstract：:An alteration in signal transduction systems in Alzheimer's disease (AD) would likely be of pathophysiological significance, because these processes control normal brain functions. Previously, a diminished beta-adrenergic-mediated cyclic AMP response was found in cultured fibroblasts from AD patients. Because cross-ta...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64020761.x
更新日期：1995-02-01 00:00:00
abstract：:The short and long forms of the D2 dopamine receptor have been expressed at similar levels in fibroblast Ltk- cells, and the long form of the receptor has also been expressed in Chinese hamster ovary cells. The ligand binding properties of the two forms of receptor expressed in different systems have been compared in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb05863.x
更新日期：1993-01-01 00:00:00
abstract：:Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of am...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62010197.x
更新日期：1994-01-01 00:00:00
abstract：:Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12352
更新日期：2013-09-01 00:00:00
