Abstract：
:: The amyloid cascade hypothesis of Alzheimer's disease envisages that the initial elevation of amyloid β-peptide (Aβ) levels, especially of Aβ(1-42) , is the primary trigger for the neuronal cell death specific to onset of Alzheimer's disease. There is now substantial evidence that brain amyloid levels are manipulable because of a dynamic equilibrium between their synthesis from the amyloid precursor protein and their removal by amyloid-degrading enzymes (ADEs) providing a potential therapeutic strategy. Since the initial reports over a decade ago that two zinc metallopeptidases, insulin-degrading enzyme and neprilysin (NEP), contributed to amyloid degradation in the brain, there is now an embarras de richesses in relation to this category of enzymes, which currently number almost 20. These now include serine and cysteine proteinases, as well as numerous zinc peptidases. The experimental validation for each of these enzymes, and which to target, varies enormously but up-regulation of several of them individually in mouse models of Alzheimer's disease has proved effective in amyloid and plaque clearance, as well as cognitive enhancement. The relative status of each of these enzymes will be critically evaluated. NEP and its homologues, as well as insulin-degrading enzyme, remain as principal ADEs and recently discovered mechanisms of epigenetic regulation of NEP expression potentially open new avenues in manipulation of AD-related genes, including ADEs.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Nalivaeva NN,Beckett C,Belyaev ND,Turner AJdoi
10.1111/j.1471-4159.2011.07510.xsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
167-85eissn
0022-3042issn
1471-4159journal_volume
120 Suppl 1pub_type
杂志文章,评审abstract：:We have examined the binding of the adenosine agonist radioligands [3N]N6-cyclohexyladenosine ([3H]CHA) and [3H]5'-N-ethylcarboxamidoadenosine ([3H]NECA) to membranes prepared from postmortem human pineal glands. The results showed that the A-1-specific ligand CHA did not bind to membranes. By contrast, [3H]NECA, a no...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb03141.x
更新日期：1990-10-01 00:00:00
abstract：:Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches c...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03661.x
更新日期：2006-04-01 00:00:00
abstract：:The content of the tryptophan metabolites quinolinic acid (QUIN), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) was measured in various brain areas of rats bearing a portocaval anastomosis (PCA) for 4 weeks, using mass fragmentography or HPLC. In these animals, the content of the excitotoxic comp...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb13052.x
更新日期：1986-03-01 00:00:00
abstract：:Challenge of protease-activated receptors induces cytosolic Ca(2+) concentration ([Ca(2+) ](c)) increase, mitogen-activated protein kinase activation and reactive oxygen species (ROS) formation with a bandwidth of responses in individual cells. We detected in this study in situ the thrombin-induced [Ca(2+) ](c) rise a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07527.x
更新日期：2011-12-01 00:00:00
abstract：:The distributions of glutamate decarboxylase (EC 4.1.1.15), gamma-aminobutyric acid transaminase (EC 2.6.1.19), and succinate semialdehyde dehydrogenase (EC 1.2.1.24) were determined in monkey retina. The decarboxylase was almost restricted to the inner plexiform layer. The transaminase was also highest in this layer,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02782.x
更新日期：1984-05-01 00:00:00
abstract：:Expression of the neurotrophin-3 (NT-3) receptor (TrkC) and the effects of NT-3 on signal transduction were investigated in highly enriched populations of embryonic rat hippocampal pyramidal neurons grown in bilaminar cultures. PCR analysis revealed that the predominant trkC isoform is K1, which lacks an insert in the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.67030952.x
更新日期：1996-09-01 00:00:00
abstract：:The metabolism and blood-brain transport of choline (Ch) were investigated in perfused canine brain under control conditions and for 60 min after inhibition of brain cholinesterases by the organophosphorus (OP) compounds soman (pinacolylmethylphosphonofluoridate). Ch and acetylcholine (ACh) in blood and brain samples ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb02993.x
更新日期：1988-03-01 00:00:00
abstract：:The hippocampal formation has been extensively research in terms of its putative neurotransmitters, anatomical connections, and behavioral relevance. An aspect of importance is the assessment of apparent neurotransmitter receptors by using receptor binding assays. In the present study, such assays were done in vitro t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb06642.x
更新日期：1982-06-01 00:00:00
abstract：:The distribution of basal and of H2O2-stimulated cyclooxygenase activity in the primary fractions of rat brain homogenates and in the subfractions of crude mitochondrial fraction was studied. For comparison, the localization of H2O2-generating monoamine oxidase (MAO) as well as that of the mitochondrial marker succina...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb11297.x
更新日期：1983-02-01 00:00:00
abstract：:Tau, a microtubule-associated protein, is encoded by a single gene, whose expression is primarily neuronal. In this work, we defined an 80-bp region of the tau promoter that confers tau protein with neuronal expression. This fragment works in conjunction with an endogenous initiation region to activate neuronal precur...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0751408.x
更新日期：2000-10-01 00:00:00
abstract：:An enzyme-linked immunoadsorbent assay (ELISA) for neurofilament protein was utilised to quantify the effect of exogenous ganglioside on neurite regeneration in cultures of dorsal root ganglion neurones. In contrast to nerve growth factor (NGF), ganglioside GM1 (100 micrograms/ml) failed to support neuronal survival a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb08752.x
更新日期：1985-04-01 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：:The synaptosomal metabolism of glutamine was studied under in vitro conditions that simulate depolarization in vivo. With [2-15N]glutamine as precursor, the [glutamine]i was diminished in the presence of veratridine or 50 mM KCl, but the total amounts of [15N]glutamate and [15N]aspartate formed were either equal to th...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb04911.x
更新日期：1990-06-01 00:00:00
abstract：:Thymosin beta 4 (Tβ4), a secreted 43 amino acid peptide, promotes oligodendrogenesis, and improves neurological outcome in rat models of neurologic injury. We demonstrated that exogenous Tβ4 treatment up-regulated the expression of the miR-200a in vitro in rat brain progenitor cells and in vivo in the peri-infarct are...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13394
更新日期：2016-01-01 00:00:00
abstract：:Diminished energy metabolism and reduced activity of brain alpha-ketoglutarate dehydrogenase complex (KGDHC) occur in a number of neurodegenerative diseases. The relation between diminished KGDHC activity and altered energy metabolism is unknown. The present study tested whether a reduction in the KGDHC activity would...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.05955.x
更新日期：2009-05-01 00:00:00
abstract：:Using antiphosphotyrosine antibodies, we have investigated protein phosphorylation in mouse brain during development in intact animals and in reaggregated cerebral cultures. Under basal conditions, in vivo and in vitro, the levels of two main phosphoproteins, of Mr 120,000 and 180,000 (pp180), increased with developme...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09751.x
更新日期：1992-02-01 00:00:00
abstract：:We used both the polymerase chain reaction (PCR) and in situ hybridization to search for the presence of proteolipid protein (PLP) gene transcripts in the developing mouse. Total brain RNA extracted from 13-19-day embryos, analyzed by PCR, demonstrated the presence of a single transcript that was unambiguously identif...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09378.x
更新日期：1992-03-01 00:00:00
abstract：:The main electric organ of Electrophorus electricus is particularly rich in thiamine triphosphate, which represents 87% of the total thiamine content in this tissue. The thiamine pyrophosphate concentration, however, is very low in the eel electric organ and skeletal muscle as compared with other eel or rat tissues. F...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb02891.x
更新日期：1987-08-01 00:00:00
abstract：:We investigated changes in the extracellular levels of acetylcholine (ACh) following local application of serotonergic agents to the dorsal hippocampus of freely moving rats by means of perfusion using a microdialysis technique. Perfusion of serotonin (5-HT; 10 microM, for 30 min at a rate of 3 microliters/min), disso...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62051804.x
更新日期：1994-05-01 00:00:00
abstract：:The γ-secretase complex is composed of at least four components: presenilin 1 or presenilin-2, nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer 2. In this study, using knockout cell lines, our data demonstrated that knockout of NCT, as well as knockout of presenilin enhancer 2, completely...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13518
更新日期：2016-03-01 00:00:00
abstract：:Molecular mechanisms underlying tauopathy remain undetermined. In the current study, single cell gene expression profiling was coupled with custom-designed cDNA array analysis to evaluate tau expression and other cytoskeletal elements within individual neuronal populations in patients with no cognitive impairment (NCI...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03641.x
更新日期：2006-03-01 00:00:00
abstract：:The present study investigated the effects of two serotonin (5-HT) uptake inhibitors, citalopram and paroxetine, and of a non-selective noradrenaline (NA) and 5-HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Ci...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03030.x
更新日期：2005-04-01 00:00:00
abstract：:The presence of serine transhydroxymethylase (STHM; EC 2.1.2.1) in crude homogenates of rat, guinea pig and goat retina has been demonstrated. There was a variation in the levels of retinal STHM activity in the three species. Substantial STHM activity was found in all the three retinal preparations in the absence of p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb07955.x
更新日期：1982-09-01 00:00:00
abstract：:We have shown recently that the presence of albumin in astrocytes triggers the synthesis and release of oleic acid, which behaves as a neurotrophic factor for neurons. Thus, oleic acid promotes axonal growth together with the expression of the axonal growth-associated protein, GAP-43. Here we attempted to elucidate wh...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02262.x
更新日期：2004-03-01 00:00:00
abstract：:Carnitine is known to accumulate in brain, therefore transport of carnitine through the blood-brain barrier was studied in an in vitro system using bovine brain capillary endothelial cells (BBCEC) grown on filter inserts in a co-culture system with glial cells. Long-term exposure of BBCEC to carnitine resulted in a hi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02752.x
更新日期：2004-11-01 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：:Choline acetyltransferase (ChAT) is specifically expressed in cholinergic neurons. To identify control mechanisms regulating the cell-specific expression of the gene encoding ChAT, transient expression of the luciferase gene driven by human ChAT gene 5'flanking sequences was compared in cholinergic and noncholinergic ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb02181.x
更新日期：1993-08-01 00:00:00
abstract：:We recently described a new protein associated exclusively with neuronal clathrin-coated vesicles (CCVs), and characterized two monoclonal antibodies that react with it (S-8G8 and S-6G7). In this report, the association of neuronal protein of 185 kilodaltons (NP185) with CCV kinases and its interaction with tubulin ar...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb10929.x
更新日期：1989-01-01 00:00:00
abstract：:The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a convergi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2012.07860.x
更新日期：2012-09-01 00:00:00
abstract：:Using a whole-cell binding procedure with long incubations at low temperature and subsequent acid stripping, we have characterized an atypical endothelin (ET) receptor in primary rat cortical astrocyte cultures. We found the following: (a) no competition for 125I-ET-1 binding by the ET(A) antagonists BQ-123 and LU 135...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70020473.x
更新日期：1998-02-01 00:00:00
