Abstract：
:Alzheimer's disease is characterized neuropathologically by the presence of neuritic and amyloid plaques, vascular amyloid, and neurofibrillary tangles in specific brain areas. The main constituent of amyloid deposits is amyloid beta protein, a 40-42 amino acid proteolytic product of the amyloid beta-precursor protein. In our search for proteases that can generate the N-terminus of amyloid beta protein (beta-secretases), we discovered a thiol-dependent metalloprotease that was identified, by peptide sequencing, as metalloendopeptidase EC 3.4.24.15. In vitro, the metalloprotease cleaves the methionine-aspartic acid bond in a 10 amino acid synthetic peptide, indicating that it could generate the N-terminus of amyloid beta protein, and generates amyloidogenic fragments from full-length recombinant amyloid beta-precursor protein. Mouse monoclonal antibodies produced against a unique synthetic peptide from the metalloprotease labeled various monkey tissues as detected by western blots and immunohistochemistry. Unexpectedly, two monoclonal antibodies, IVD6 and IIIF3, immunolabeled strongly intracellular neurofibrillary tangles, neurites of senile plaques, and neuropil threads, but not "ghost" tangles or amyloid in sections taken from Alzheimer's disease brain. This finding provides further evidence for the metalloprotease's relevance to Alzheimer's disease pathology, although the connection between tangle staining and the formation of amyloid beta protein remains to be elucidated.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Conn KJ,Pietropaolo M,Ju ST,Abraham CRdoi
10.1046/j.1471-4159.1996.66052011.xsubject
Has Abstractpub_date
1996-05-01 00:00:00pages
2011-8issue
5eissn
0022-3042issn
1471-4159journal_volume
66pub_type
杂志文章abstract：:Presynaptic nicotinic acetylcholine receptors on striatal nerve terminals modulate the release of dopamine. We have compared the effects of a number of nicotinic agonists and antagonists on a perfused synaptosome preparation preloaded with [3H]dopamine. (-)-Nicotine, acetylcholine, and the nicotinic agonists cytisine ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb02341.x
更新日期：1990-03-01 00:00:00
abstract：:Primary neuronal cultures from 8-day-old rat cerebellum were incubated in the presence of exogenously added 16 nM [gamma-32P]ATP. Phosphorylation of a 45-kDa endogenous protein was detected within 1 min and increased linearly for approximately 20 min. Unlike what was seen with [gamma-32P]ATP, in the presence of [32P]o...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63062028.x
更新日期：1994-12-01 00:00:00
abstract：:The effects of heat stress on protein synthesis and fast axonal transport were examined in an in vitro bullfrog primary afferent neuron preparation. The magnitude of effect was determined for individual [35S]methionine-labelled protein species separated via two-dimensional gel electrophoresis. Elevation of temperature...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb01833.x
更新日期：1988-09-01 00:00:00
abstract：:Previous studies have purified from brain a Ca2+/calmodulin-dependent protein kinase II (designated CaM-kinase II) that phosphorylates synapsin I, a synaptic vesicle-associated phosphoprotein. CaM-kinase II is composed of a major Mr 50K polypeptide and a minor Mr 60K polypeptide; both bind calmodulin and are phosphory...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb06084.x
更新日期：1984-12-01 00:00:00
abstract：:The binding of [3H]5-hydroxytryptamine (5-HT, serotonin) to cerebellar membranes was examined after preincubation of [3H]5-HT in the presence or absence of ascorbate. The tissue preparation was identical in all experiments and consisted of rat cerebellar homogenates in Tris-HCl buffer with 0.1% ascorbate. Cerebellar m...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb02828.x
更新日期：1986-07-01 00:00:00
abstract：:The effects of the protein kinase inhibitor H-7 on early and delayed responses to nerve growth factor (NGF) were investigated in PC12 cells. H-7 reduced the NGF-induced expression of c-Fos in a dose-dependent manner without affecting the time course of c-Fos appearance. Conversely, H-7 potentiated delayed NGF effects,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62020479.x
更新日期：1994-02-01 00:00:00
abstract：:Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybri...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb06336.x
更新日期：1981-12-01 00:00:00
abstract：:Action mechanism of lipopolysaccharide (LPS), interleukin-1β (IL-1β), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1β resulte...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07188.x
更新日期：2011-04-01 00:00:00
abstract：:Aromatic L-amino acid decarboxylase (AAAD) activity of the rat retina increases when animals are placed in a lighted environment from the dark. The rise of activity can be inhibited by administering alpha 2 adrenoceptor agonists. In the dark, the enzyme activity can be made to increase by administering alpha 2 adrenoc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb09169.x
更新日期：1989-02-01 00:00:00
abstract：:Epinephrine (Epi) mediates various physiological effects via alpha2A-adrenergic receptors (alpha2A-ARs). Studies in mice with a point mutation in the gene for alpha2A-AR have shown that these receptors are responsible for the centrally mediated depressor effects of alpha2-AR agonists. These studies underscore the impo...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70010086.x
更新日期：1998-01-01 00:00:00
abstract：:The time course of Ca2+-dependent [3H]acetylcholine [( 3H]ACh) release and inactivation of 45Ca2+ entry were examined in rat brain synaptosomes depolarized by 45 mM [K+]0. Under conditions where the intrasynaptosomal stores of releasable [3H]ACh were neither exhausted nor replenished in the course of stimulation, the ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb04820.x
更新日期：1983-09-01 00:00:00
abstract：:The in vivo biosynthesis of cholecystokinin (CCK) in subcortical regions of the rat brain was studied by intracisternal pulse injections of [35S]methionine. The rats were killed 1.0 or 1.5 h after the injection. Subcortical CCK extracted in boiling water and acetic acid was immunoabsorbed by an antiserum specific for ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb06290.x
更新日期：1980-08-01 00:00:00
abstract：:Coordinate secretion of two prohormone/proneuropeptide processing enzymes [pro-opiomelanocortin converting enzyme (PCE) and an aminopeptidase B-like enzyme (APBE)] and alpha-melanotropin (alpha-MSH) from bovine intermediate lobe pituitary cells was studied. Stimulation of secretion with 8-bromo-cyclic AMP produced sig...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb09217.x
更新日期：1989-05-01 00:00:00
abstract：:The [14C]deoxyglucose [Sokoloff et al., J. Neurochem. 28, 897-916 (1977)] and [6-14C]glucose [Hawkins et al., Am. J. Physiol. 248, C170-C176 (1985)] quantitative autoradiographic methods were used to measure regional brain glucose utilization in awake rats. The spatial resolution and qualitative appearance of the auto...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb01028.x
更新日期：1987-11-01 00:00:00
abstract：:We report on the expression of ionotropic glutamate receptor subunits in primary neuronal cultures from rat cortex, hippocampus and cerebellum and of metabotropic glutamate (mGlu) receptor subtypes in these neuronal cultures as well as in cortical astroglial cultures. We found that the NMDA receptor (NR) subunits NR1,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00369.x
更新日期：2001-06-01 00:00:00
abstract：:Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an "atypical" neuroleptic, is a selective antagonist of D2...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb02910.x
更新日期：1987-08-01 00:00:00
abstract：:Arg0-Met5-enkephalin (Arg0-MEK) was isolated from bovine striatum and purified to homogeneity. The peptide was extracted with trichloroacetic acid, followed by column chromatography successively on Bio-Sil C8, semipreparative HPLC Radial-Pak C18, fast protein liquid chromatography (FPLC) Mono S, HPLC Ultrasphere-ODS, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63051748.x
更新日期：1994-11-01 00:00:00
abstract：:Male copulatory behavior in the snail Lymnaea stagnalis is controlled by several types of peptidergic neurons, including a cluster of neurons in the ventral lobe of the right cerebral ganglion that show immunoreactivity to myomodulin-A of Aplysia and innervate the penis complex. We identified structurally myomodulin-A...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66010321.x
更新日期：1996-01-01 00:00:00
abstract：:Tubulin tyrosine ligase catalyzes the reversible addition of tyrosine to the C-terminus of tubulin alpha chains. By using ligase and carboxypeptidase A in conjunction, we have previously shown that brain cytoplasmic tubulin exists in three forms: 15-40% already has C-terminal tyrosine, another 10-30% can accept additi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb03708.x
更新日期：1980-09-01 00:00:00
abstract：:We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs) such as glutamate, N-methyl-D-aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate caused an increase in the inositol 1,4,5-trisphosphate formation and the intracellular C...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63041346.x
更新日期：1994-10-01 00:00:00
abstract：:Beta-carbolines have been suggested to be involved in the pathogenesis of Parkinson's disease as a result of their structural similarity to the neurotoxin N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The chloral-derived beta-carboline derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) caus...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.00875.x
更新日期：2002-05-01 00:00:00
abstract：:In the rat parotid gland, substance P has been shown to induce a phosphatidylinositol bisphosphate breakdown resulting in an inositol trisphosphate production. These data suggested that substance P activated a phospholipase C and thus mediated its effects through the calcium-phospholipid pathway. To determine which ne...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb10980.x
更新日期：1992-06-01 00:00:00
abstract：:The endocannabinoid anandamide (N-arachidonoylethanolamine) and other bioactive long-chain N-acylethanolamines are thought to be formed from their corresponding N-acylphosphatidylethanolamines by a specific phospholipase D (NAPE-PLD) in the brain as well as other tissues. However, regional distribution of NAPE-PLD in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03234.x
更新日期：2005-08-01 00:00:00
abstract：:The mechanism of attachment of acetylcholinesterase (AChE) to neuronal membranes in interneuronal synapses is poorly understood. We have isolated, sequenced, and cloned a hydrophobic protein that copurifies with AChE from human caudate nucleus and that we propose forms a part of a complex of membrane proteins attached...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0742146.x
更新日期：2000-05-01 00:00:00
abstract：:In this study, we show specific intracellular responses evoked by the stimulation of astrocytes with the P1,P5-di(adenosine-5')pentaphosphate, Ap5A. The stimulation of astrocytes with micromolar concentrations of the dinucleotide elicited rapid increases in intracellular calcium concentration ([Ca2+]i), showing an EC5...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01111.x
更新日期：2002-10-01 00:00:00
abstract：:We have previously shown that the [3H]saxitoxin binding site of the sodium channel is expressed independently of the [125I]scorpion toxin binding site in chick muscle cultures and in rat brain. In the present work, we studied the development of the sodium channel protein during chemically induced differentiation of N1...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05656.x
更新日期：1987-04-01 00:00:00
abstract：:Rotating disk electrode voltammetry at glassy carbon electrodes and ultraviolet/visible spectroscopy were used to demonstrate that dopamine binds to neurotensin with a dissociation constant of 7.5 x 10(-8). By measuring the binding constants of various neurotensin analogs, it was found that the -Arg8-Arg9-portion of t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb01965.x
更新日期：1990-04-01 00:00:00
abstract：:Antisera raised to the 68,000, 145,000 and 200,000 molecular weight subunits of rat neurofilaments were used for immunochemical staining of polypeptides separated by one- and two-dimensional gel electrophoresis. It was found that each antiserum reacts intensely with its corresponding neurofilament subunit and weakly w...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb04676.x
更新日期：1981-11-01 00:00:00
abstract：:5-Hydroxytryptamine2 (5-HT2) receptor antagonists have been shown to interfere with the stimulation of striatal dopamine synthesis and release produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). To localize the receptors responsible for the attenuation of MDMA-induced release, 5-HT2 receptor...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62041382.x
更新日期：1994-04-01 00:00:00
abstract：:We have identified a novel mouse gene named pancortin that is expressed dominantly in the mature cerebral cortex. This gene produces four different species of proteins, Pancortin-1-4, sharing a common region in the middle of their structure with two variations at the N-terminal (A1 or A2 part) and C-terminal (C1 or C2...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750001.x
更新日期：2000-07-01 00:00:00
