Abstract:
:Considerable evidence indicates that the amyloid-beta (Abeta) peptide, a proteolytic fragment of the amyloid precursor protein, is the pathogenic agent in Alzheimer's disease (AD). A number of proteases have been reported as capable of degrading Abeta, among them: neprilysin, insulin-degrading enzyme, endothelin-converting enzyme-1 and -2, angiotensin-converting enzyme and plasmin. These proteases, originating from a variety of cell types, degrade Abeta of various conformational states and in different cellular locations. We report here the isolation of a serine protease from serum-free conditioned medium of human neuroblastoma cells. Tandem mass spectrometry (MS/MS)-based sequencing of the isolated protein identified acyl peptide hydrolase (APH; EC3.4.19.1) as the active peptidase. APH is one of four members of the prolyl oligopeptidase family of serine proteases expressed in a variety of cells and tissues, including erythrocytes, liver and brain, but its precise biological activity is unknown. Here, we describe the identification of APH as an Abeta-degrading enzyme, and we show that the degradation of Abeta by APH isolated from transfected cells is inhibited by APH-specific inhibitors, as well as by synthetic Abeta peptide. In addition, we cloned APH from human brain and from neuroblastoma cells. Most importantly, our results indicate that APH expression in AD brain is lower than in age-matched controls.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Yamin R,Bagchi S,Hildebrant R,Scaloni A,Widom RL,Abraham CRdoi
10.1111/j.1471-4159.2006.04251.xsubject
Has Abstractpub_date
2007-01-01 00:00:00pages
458-67issue
2eissn
0022-3042issn
1471-4159pii
JNC4251journal_volume
100pub_type
杂志文章abstract::Methylphenidate (MPD) was found to inhibit competitively the striatal dopamine transporter (DAT) and bind at sites on the DAT in common with both cocaine (a non-substrate site ligand) and amphetamine (a substrate site ligand). Some methylphenidate analogues modified on the aromatic ring and/or at the nitrogen were tes...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0721266.x
更新日期:1999-03-01 00:00:00
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...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12288
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb02557.x
更新日期:1991-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1991-11-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb06104.x
更新日期:1984-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1987-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb08350.x
更新日期:1992-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01925.x
更新日期:2003-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02570.x
更新日期:2004-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb05316.x
更新日期:1981-07-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00015.x
更新日期:2001-01-01 00:00:00
abstract::Although myelin oligodendrocyte glycoprotein is a candidate autoantigen in multiple sclerosis, its function remains unknown. In humans, mRNA expressed by the myelin oligodendrocyte glycoprotein gene is alternatively spliced resulting in at least nine unique protein isoforms. In this study, we investigated the sub-cell...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04687.x
更新日期:2007-09-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00729.x
更新日期:1986-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04958.x
更新日期:2007-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0751590.x
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abstract::We addressed the balance between thrombin and its serpin protease nexin I (PNI) after sciatic nerve injury in the mouse. Prothrombin levels increased twofold 24 h after nerve crush, as measured by a specific chromogenic assay, and peaked at day 3. Thrombin activity also increased 2-4 days after injury in distal sciati...
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pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67052188.x
更新日期:1996-11-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2007-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69052220.x
更新日期:1997-11-01 00:00:00
abstract::We have examined the ability of KW-6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of L-DOPA in 6-hydroxydopamine-lesioned rats. In animals rendered dyskinetic by a previous course of L-DOPA treatment, KW-6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.01632.x
更新日期:2003-03-01 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::Microscopic fluorescence analysis of fura-2-loaded bovine adrenal chromaffin cells demonstrates that approximately 70% of the cells responded to arachidonic acid in increasing the intracellular Ca2+ concentration. Because this increase was markedly less in the absence of external Ca2+, we examined the effect of arachi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb09830.x
更新日期:1993-11-01 00:00:00
abstract::This study investigated mRNA expression and protein localization of equilibrative and concentrative nucleoside transporters (ENTs, CNTs) in primary cultures of rat brain endothelial cells (RBEC) and rat choroid plexus epithelial cells (RCPEC). Reverse transcriptase PCR analysis revealed that RBEC and RCPEC contained m...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03312.x
更新日期:2005-09-01 00:00:00
abstract::The P2Y11 nucleotide receptor detects high extracellular ATP concentrations. Mutations of the human P2RY11 gene can play a role in brain autoimmune responses, and the P2Y11 receptor alanine-87-threonine (A87T) polymorphism has been suggested to affect immune-system functions. We investigated receptor functionality of ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12666
更新日期:2014-05-01 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::Tissue plasminogen activator (tPA) administration beyond 4.5 h of stroke symptoms is beneficial for patients but has an increased risk of cerebral hemorrhage. Thus, increasing the therapeutic window of tPA is important for stroke recovery. We previously showed that prothymosin alpha (ProTα) or its mimetic hexapeptide ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14858
更新日期:2020-06-01 00:00:00
abstract::One of the fundamental goals of lipidomics research is to identify the linkage of an individual gene with a given lipidome, thereby revealing the role of that gene in lipid metabolism, transport, and homeostasis. In this study, we have identified four apolipoprotein E (apoE)-induced alterations in the lipidome of mous...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04342.x
更新日期:2007-04-01 00:00:00
abstract::Cell and tissue concentrations of NO2- and NO3- are important indicators of nitric oxide synthase activity and crucial in the regulation of many metabolic functions, as well as in nonenzymatic nitric oxide release. We adapted the capillary electrophoresis technique to quantify NO2- and NO3- levels in single identified...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69010110.x
更新日期:1997-07-01 00:00:00