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 efflux transporters with very broad specificity that are responsible for much of the efflux transport. This review focuses on three such transporters: organic acid transporter-3, peptide transporter-2 and P-glycoprotein for which there is substantial new information including 'knockout' models in mice and, in one case, dogs. Moreover, the structural biology and transport mechanism of P-glycoprotein at 3.8 angstroms is described. The overall objective is to show how this new knowledge provides a more thorough understanding (e.g., of molecular mechanisms) of efflux transport and in several cases leads to clinically relevant information that allows better treatment of certain CNS disorders (e.g., meningitis and brain cancer).
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Spector Rdoi
10.1111/j.1471-4159.2009.06451.xsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
13-23issue
1eissn
0022-3042issn
1471-4159pii
JNC6451journal_volume
112pub_type
杂志文章,评审abstract::To provide insights into the effects of temporary focal ischemia on the function of neurons and astrocytes in vivo, we measured the incorporation of radiolabel from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h....
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03778.x
更新日期:2006-05-01 00:00:00
abstract::Painful neuropathy is one of the most serious complications of diabetes and remains difficult to treat. The muscarinic acetylcholine receptor (mAChR) agonists have a profound analgesic effect on painful diabetic neuropathy. Here we determined changes in T-type and high voltage-activated Ca(2+) channels (HVACCs) and th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07456.x
更新日期:2011-11-01 00:00:00
abstract::Angiopoietin-1, an angiogenic factor, stabilizes brain microvessels through Tie-2 receptor tyrosine kinase. In traumatic brain injury, blood-brain barrier (BBB) disruption is an aggravating factor that induces brain edema and neuroinflammation. We previously showed that BQ788, an endothelin ETB receptor antagonist, pr...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.14957
更新日期:2020-08-01 00:00:00
abstract::Neuromelanin is a dark brown pigment present at high concentrations in dopaminergic neurones of the human substantia nigra (SN). Early electron microscopic examinations of neuromelanin fine structure revealed a significant neutral lipid component; however, the identity of this lipid has remained unknown. Here we show ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02975.x
更新日期:2005-02-01 00:00:00
abstract::We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1 affects secretory vesicle exocytosis and quantal release kinetics remain unknown. Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells and...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12086
更新日期:2013-02-01 00:00:00
abstract::Neurite formation involves coordinated changes between the actin cytoskeleton and the microtubule network. Rho GTPases are clearly implicated in several aspects of neuronal development and function. Indeed, RhoA is a negative regulator of neurite outgrowth and its effector Rho-kinase mediates the Rho-driven neurite re...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06526.x
更新日期:2010-02-01 00:00:00
abstract::To assess the postmortem stability of brain 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) levels, groups of rats and mice were killed by cervical dislocation and left at either 21 degrees or 4 degrees C for intervals of up to 24 h until removal and freezing of whole brain...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb01679.x
更新日期:1981-03-01 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::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::beta-Amyloid peptides (Abeta40 and Abeta42) are the major constituents of amyloid plaques, which are one of the hallmarks of Alzheimer's disease (AD). The Abeta is derived from sequential cleavages of amyloid precursor protein (APP) by beta- and gamma-secretases. gamma-Secretase consists of at least four proteins wher...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03528.x
更新日期:2006-01-01 00:00:00
abstract::Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. Maintenance of NSPC multipotency is promoted by low oxygen tension, although the metabolic underpinnings of this trait have not been described. In this study, we inve...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12204
更新日期:2013-05-01 00:00:00
abstract::Spinal cord injury (SCI) elicits a neuroinflammatory reaction dominated by microglia and monocyte-derived macrophages (MDM). Because MDM do not infiltrate the spinal cord until days after injury, it may be possible to control whether they differentiate into neuroprotective or neurotoxic effector cells. However, doing ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04617.x
更新日期:2007-08-01 00:00:00
abstract::beta-Adrenergic receptor subtypes, beta 1 and beta 2, were studied during pre- and postnatal development in the rat brain. [125I]Iodocyanopindolol (6-300 pmol/L) binding assays in the presence of 5-hydroxytryptamine (0.6-6 mumol/L) were used to measure exclusively beta-adrenergic receptors. In forebrain tissue, satura...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb08235.x
更新日期:1991-09-01 00:00:00
abstract::The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neurop...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01224.x
更新日期:2002-12-01 00:00:00
abstract::The biggest risk factor for Alzheimer's disease is the process of ageing, but the mechanisms that lead to the manifestation of the disease remain to be elucidated. Why age triggers the disease is unclear but an emerging theme is the inability for a cell to efficiently maintain many key processes such as energy product...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2011.07500.x
更新日期:2012-01-01 00:00:00
abstract::Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentrati...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62031039.x
更新日期:1994-03-01 00:00:00
abstract::Exposure of bovine chromaffin cells in primary culture to 0.01-1 microM reserpine caused a dose- and time-dependent increase in intracellular levels of the amidated enkephalin peptide metorphamide. Maximal levels (approximately 800% of control) were obtained at 0.1 microM reserpine and increased levels were apparent b...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb01790.x
更新日期:1986-05-01 00:00:00
abstract::Progress has been made in Guillain-Barré syndrome, a post-infectious autoimmune neuropathy, especially on identifying Campylobacter jejuni genes responsible for the development and determinant of clinical features. C. jejuni strains carrying a sialyltransferase gene (cst-II), which is essential for the biosynthesis of...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2007.04707.x
更新日期:2007-11-01 00:00:00
abstract::To explore the hypothesis that alterations in cellular membrane lipids are present at the stage of pre-clinical Alzheimer's disease (AD) (i.e., cognitively normal at death, but with AD neuropathology), we performed targeted shotgun lipidomics of lipid extracts from post-mortem brains of subjects with pre-clinical AD. ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12368
更新日期:2013-12-01 00:00:00
abstract::Specific antisera were raised against the A and B chains of glycoprotein III. Immunoblotting revealed that in adrenal medulla both chains migrate very closely together in two-dimensional electrophoresis. Both chains with slightly differing molecular sizes are found in several endocrine tissues and in brain, kidney, li...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb13645.x
更新日期:1993-10-01 00:00:00
abstract::Abnormal regulation of brain glycogen metabolism is believed to underlie insulin-induced hypoglycaemia, which may be serious or fatal in diabetic patients on insulin therapy. A key regulator of glycogen levels is glycogen targeted protein phosphatase 1 (PP1), which dephosphorylates and activates glycogen synthase (GS)...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07345.x
更新日期:2011-08-01 00:00:00
abstract::Although transient receptor potential (TRP) channels expressed in the spinal substantia gelatinosa play a role in modulating nociceptive transmission, their properties have not been fully examined yet. In order to address this issue, the effects of 1,8-cineole and its stereoisomer 1,4-cineole on excitatory transmissio...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13433
更新日期:2016-02-01 00:00:00
abstract::A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-[2,3-3H]aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Sub...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb08125.x
更新日期:1983-06-01 00:00:00
abstract::Several neurodegenerative disorders are associated with evidence of inflammation, one feature of which is increased activation of microglia, the most likely cellular source of inflammatory cytokines like interleukin-1beta. It is now recognized that interaction of microglia with other cells contributes to maintenance o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2009.06253.x
更新日期:2009-09-01 00:00:00
abstract::In vivo microdialysis was used to determine the extent to which ionotropic glutamate receptors in the ventral tegmental area (VTA) regulate dopamine release in the nucleus accumbens. Coapplication of 2-amino-5-phosphonopentanoic acid (AP5; 200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) to the V...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65031407.x
更新日期:1995-09-01 00:00:00
abstract::Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder of unknown etiology. We hypothesized that mitochondrial DNA (mtDNA) aberration could occur in this disease and contribute to its pathogenesis. To address this we created transmitochondrial cytoplasmic hybrid (cybrid) cell lines expressing mi...
journal_title:Journal of neurochemistry
pub_type: 临床试验,杂志文章
doi:10.1046/j.1471-4159.2000.0751681.x
更新日期:2000-10-01 00:00:00
abstract::Mitochondrial dysfunction and oxidative stress are known to occur following acute seizure activity but their contribution during epileptogenesis is largely unknown. The goal of this study was to determine the extent of mitochondrial oxidative stress, changes to redox status, and mitochondrial DNA (mtDNA) damage during...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.07013.x
更新日期:2010-12-01 00:00:00
abstract::The postsynaptic density (PSD) is an electron-dense structure located at the synaptic contacts between neurons. Its considerable complexity includes cytoskeletal and scaffold proteins, receptors, ion channels and signaling molecules, in line with the role of PSDs in signal transduction and processing. The phosphorylat...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02943.x
更新日期:2005-03-01 00:00:00
abstract::Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical stimulation of th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.69020791.x
更新日期:1997-08-01 00:00:00
abstract::Phospholipase A2 (PLA2) is the name for the class of lipolytic enzymes that hydrolyze the acyl group from the sn-2 position of glycerophospholipids, generating free fatty acids and lysophospholipids. The products of the PLA2-catalyzed reaction can potentially act as second messengers themselves, or be further metaboli...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1046/j.1471-4159.1997.69030889.x
更新日期:1997-09-01 00:00:00