Abstract：
:Amyloid beta (Aβ) peptide is the major constituent of the extracellular amyloid plaques deposited in the brains of Alzheimer's disease patients and is central to the pathogenic pathway causing this disease. The identity of the neurotoxic Aβ species remains elusive. We previously reported that Aβ toxicity correlates strongly with its neuronal cell binding leading us to hypothesize that neuronal cell death is caused by the binding of a specific oligomeric Aβ species. To identify the specific oligomeric Aβ species that is associated with cell death, we treated mouse cortical neuronal cultures with synthetic Aβ40 and Aβ42 peptides and identified that the cellular Aβ binding and neurotoxicity were time and concentration dependent. We found a significant correlation between the amount of trimer and tetramer species bound to neurons with increasing neurotoxicity. We prepared Aβ40 oligomers (up to tetramers) using photo-induced cross-linking of unmodified peptides to confirm this oligomer-specific neurotoxic activity. Our results identify the Aβ tetramer, followed by the trimer, as the most toxic low-order oligomers Aβ species. Our findings suggested that binding of amyloid-β (Aβ) tetramer and trimer, not monomer or dimer, to neurons is critical to induce neuronal cell death associated with Alzheimer's Disease. We proposed that Aβ trimer and tetramer are the potential neurotoxic Aβ species. This would provide more specific therapeutic target for Alzheimer's Disease.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Jana MK,Cappai R,Pham CL,Ciccotosto GDdoi
10.1111/jnc.13443subject
Has Abstractpub_date
2016-02-01 00:00:00pages
594-608issue
3eissn
0022-3042issn
1471-4159journal_volume
136pub_type
杂志文章abstract：:We have investigated the effects of fetal hypophysectomy (HX) with or without thyroxine (T4)replacement on the plasma concentrations of free methionine-enkephalin (free Met-Enk), noradrenaline, and adrenaline in late gestation sheep fetus. Plasma adrenaline concentrations were significantly higher in intact fetal shee...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63041386.x
更新日期：1994-10-01 00:00:00
abstract：:Although alterations in serotonin levels and neurotransmission are associated with depressive disorders and effective antidepressant therapy, the exact cause of these disorders and the mode of action of antidepressant drugs are poorly understood. In a genetic rat model of depression [Flinders sensitive line (FSL) rats...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69062477.x
更新日期：1997-12-01 00:00:00
abstract：:Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene may contribute to the development of Parkinson's disease. The purpose of this study was to determine if selective loss of nigrostriata...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06497.x
更新日期：2010-02-01 00:00:00
abstract：:The effects of gamma-aminobutyric acid (GABA) on the spontaneous release of endogenous glutamic acid (Glu) or aspartic acid (Asp) and the effects of Glu on the release of endogenous GABA or [3H]GABA were studied in superfused rat cerebral cortex synaptosomes. GABA increased the outflow of Glu (EC50 17.2 microM) and As...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03558.x
更新日期：1993-07-01 00:00:00
abstract：:Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by th...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0742067.x
更新日期：2000-05-01 00:00:00
abstract：:Cavernous angiomas are vascular malformations that cause neurodegeneration and symptoms including epileptiform seizures, headache, and motor deficits. Following neurosurgical removal of the angiomas, patients mostly recover well and become seizure-free. This study reports on the levels of certain amino acids in angiom...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.67010260.x
更新日期：1996-07-01 00:00:00
abstract：:This article is a critique of the paper by Khairnar et al. in the current issue of the Journal of Neurochemistry which describes the use of a sophisticated magnetic resonance imaging technique, diffusion kurtosis imaging, to investigate microstructural changes in the brain of TNWT-61 mice that are over-expressing α-sy...
journal_title：Journal of neurochemistry
pub_type： 社论
doi：10.1111/jnc.13522
更新日期：2016-03-01 00:00:00
abstract：:Malonaldehyde formation by cortical brain slices from rat brain was determined as a function of incubation time and of oxygen pressure. This substance, a byproduce of lipid peroxidation, was detected by the thiobarbituric acid test. Significant amounts of malonaldehyde were formed by brain slices during incubation in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb09022.x
更新日期：1980-12-01 00:00:00
abstract：:The F3 molecule is a member of the immunoglobulin superfamily anchored to plasma membranes by a glycosylphosphatidylinositol group. In adult mouse cerebellum, F3 is predominantly expressed on a subset of axons, the parallel fibers, and at their synapses. In vitro studies established that it is a plurifunctional molecu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65052307.x
更新日期：1995-11-01 00:00:00
abstract：:Oxidative stress and free radical damage have been implicated in the neurodegenerative changes characteristic of several neurodegenerative diseases, including Alzheimer's disease. There is experimental evidence that the neurotoxicity of beta-amyloid is mediated via free radicals, and as the deposition of beta-amyloid ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.68041590.x
更新日期：1997-04-01 00:00:00
abstract：:Both phosphointermediate- and vacuolar-type (P- and V-type, respectively) ATPase activities found in cholinergic synaptic vesicles isolated from electric organ are immunoprecipitated by a monoclonal antibody to the SV2 epitope characteristic of synaptic vesicles. The two activities can be distinguished by assay in the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb11331.x
更新日期：1992-04-01 00:00:00
abstract：:The kinetic properties of soluble tyrosine hydroxylase from rat striatum and the activation of the enzyme by the polyanion heparin were assessed as a function of the monovalent cations K+, Na+, tetramethylammonium (TMA+), and Tris. Substitution of K+ or Na+ for TMA+ or Tris can alter the kinetic properties of tyrosine...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb12541.x
更新日期：1981-09-01 00:00:00
abstract：:There is extensive experimental evidence indicating a crucial role for glutamate in epileptogenesis and epileptic activity. The glial glutamate transporters GLT1 and GLAST are proposed to account for the majority of extracellular glutamate re-uptake. In the present study, polyclonal antibodies specific to GLT1 and GLA...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00612.x
更新日期：2001-11-01 00:00:00
abstract：:Using tritium-labelled 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) its tissue distribution and metabolism were investigated in adult mice and 4-day-old chicks after systemic administration of the drug. It was found not to be significantly metabolized in the brain since metabolites of THPO corresponding to on...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb00676.x
更新日期：1986-09-01 00:00:00
abstract：:In Aplysia, serotonin mediates behavioral sensitization by increasing the strength of the synapse between sensory and motor neurons, a process known as facilitation. The retention of long-term facilitation is blocked by rapamycin, an inhibitor of a specific translational pathway. One possible rapamycin-sensitive targe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02634.x
更新日期：2004-09-01 00:00:00
abstract：:The murine neuroblastoma N1E-115 cell line possesses a high density of angiotensin II (AngII) receptors that can be solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. These solubilized binding sites exhibited high affinity for CGP-42112A and not Losartan, indicating ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62062106.x
更新日期：1994-06-01 00:00:00
abstract：:Glycogen synthase kinase 3 (GSK3) plays important roles in Wnt and insulin signaling, cell fate determination, and Alzheimer-like tau phosphorylation. We discovered an isoform of tau protein kinase I (TPKI)/GSK3beta with a 13 amino acid insert in the catalytic domain owing to alternative splicing. The alternative tran...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.00918.x
更新日期：2002-06-01 00:00:00
abstract：:Attempts were made to label tachykinin NK2 binding sites in the adult rat brain using [125I]neurokinin A (NKA) as ligand in the presence of NK1 and NK3 agonist or antagonist to avoid labelling of NK1 and NK3 binding sites, respectively. A high-affinity, specifically NK2-sensitive, [125I]NKA-binding, temperature-depend...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00633.x
更新日期：2001-12-01 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：:Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Here, we investigated the effect of peroxide exposure on the expression of genes coding for cytoplasmic and endoplasmic reticulum (ER) stress proteins. Primary neuronal cell cultures were exp...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00206.x
更新日期：2001-03-01 00:00:00
abstract：:Multiple lines of evidence implicate lysosomes in a variety of pathogenic events that produce neurodegeneration. Genetic mutations that cause specific enzyme deficiencies account for more than 40 lysosomal storage disorders. These mostly pre-adult diseases are associated with abnormal brain development and mental reta...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1046/j.1471-4159.2002.01192.x
更新日期：2002-11-01 00:00:00
abstract：:cDNAs encoding four isoforms of the human NMDA receptor (NMDAR) NMDAR2C (hNR2C-1, -2, -3, and -4) have been isolated and characterized. The overall identity of the deduced amino acid sequences of human and rat NR2C-1 is 89.0%. The sequences of the rat and human carboxyl termini (Gly925-Val1,236) are encoded by differe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71051953.x
更新日期：1998-11-01 00:00:00
abstract：:As a basis for attempts to define the structures of the proteins within myelin, methods have been developed for their extraction and isolation in solutions of non-denaturing detergents. With use of solutions of deoxycholate or Triton X-100, up to 90% of the protein has been extracted from bovine CNS myelin, along with...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02679.x
更新日期：1984-02-01 00:00:00
abstract：:We investigated [(18)F]fluoroethyl-harmol ([(18)F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO-A). Binding of [(18)F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction w...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13370
更新日期：2015-12-01 00:00:00
abstract：:The ontogeny of muscarinic receptors was studied in human fetal striatum, brainstem, and cerebellum to investigate general principles of synaptogenesis as well as the physiological balance between various chemical synapses during development in a given region of the brain. [3H]Quinuclidinyl benzilate ([3H]QNB) binding...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb10555.x
更新日期：1985-12-01 00:00:00
abstract：:We investigated by 13C NMR the turnover of the H3 deuterons of (2-13C) glutamate and (2-13C) glutamine in the brain of partially deuterated rats. Adult animals (150-200 g) fed ad libitum received 50% 2H2O or tap water 9 days before infusing (1-13C) glucose or (2-13C) acetate for 5, 10, 15, 30, 60, or 90 min. The brain...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.05962.x
更新日期：2009-05-01 00:00:00
abstract：:Environmental regulation of sensory function has provided an important model of plastic mechanisms mediating neural information processing. To define potential commonalities in information processing in different systems, we investigated molecular changes elicited by sensory deprivation in the developing rat olfactory...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb13410.x
更新日期：1993-05-01 00:00:00
abstract：:Modulation of acetylcholine (ACh) release from superfused hippocampal slices was examined when the release of ACh was stimulated by exposure of slices to elevated K+ concentration. Evoked release was not sensitive to inhibition by 0.1 microM tetrodotoxin, but it could be inhibited in a dose-dependent manner by a musca...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb05799.x
更新日期：1990-12-01 00:00:00
abstract：:The Na+-dependent glutamate/aspartate transporter GLAST plays a major role in the removal of glutamate from the synaptic cleft. Short-term, as well as long-term changes in transporter activity are triggered by glutamate. An important locus of regulation is the density of transporter molecules present at the plasma mem...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02706.x
更新日期：2004-10-01 00:00:00
abstract：:Both adenosine and interleukin-6 (IL-6) have been implicated in the pathophysiology of, e.g., epileptic seizures, traumatic brain injury, and affective disorders. Stimulation of adenosine A2B receptors on astrocytes in vitro leads to the increased synthesis and secretion of IL-6. We investigated whether or not activat...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.05191.x
更新日期：2008-05-01 00:00:00
