Abstract:
:The recent publication of the human genome sequence provides an opportunity both to combat diseases that are presently considered as pharmaceutically intractable and also to improve current therapies for many common human diseases. The identification of every human gene by ongoing bioinformatic efforts has the potential, when combined with functional genomic approaches, to pinpoint the molecular basis of every human disease, and to discover appropriate intervention points. This exciting prospect is directly relevant to the successful development of effective therapeutics because the past record of drug discovery suggests that 30%-40% of experimental drugs fail because an inappropriate biological target was pursued. The major impact of genomic information may therefore be to reduce this biological failure rate by earlier definition of drug targets related to disease susceptibility or progression. This paper briefly reviews some of the approaches that can be used to identify biologically relevant drug targets.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Butcher SPdoi
10.1023/a:1022349805831keywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
367-71issue
2eissn
0364-3190issn
1573-6903journal_volume
28pub_type
杂志文章,评审abstract::Memory impairment is a major problem afflicting mankind. The association between memory functions and neurotransmitter functions is of great interest for understanding brain function. Serotonergic pathways play an important role in the modulation of memory functions but the importance of its receptor types and subtype...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-012-0839-5
更新日期:2012-10-01 00:00:00
abstract::A number of recent findings support the notion of mechanistic parallels between Alzheimer disease (AD) and oncogenic processes, specifically, that neurons in AD, like cancer cells, display aberrant mitotic cell cycle re-entry. However, the mechanism that drives postmitotic neurons to reenter cell cycle remains elusive...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-006-9146-3
更新日期:2007-04-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an adult-onset, irreversible neurodegenerative disease that leads to progressive paralysis and inevitable death 3-5 years after diagnosis. The mechanisms underlying this process remain unknown, but new evidence indicates that accumulating levels of D-serine result from the downre...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-016-2131-6
更新日期:2017-04-01 00:00:00
abstract::The present study has attempted to elucidate the alteration of serotonin turnover after 24 h REM sleep deprivation in different regions in brain of young rat. Sleep deprivation was induced by the inverted flower pot technique. Results of this study show increased serotonin turnover after 24 h REM sleep deprivation in ...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-005-9139-7
更新日期:2006-01-01 00:00:00
abstract::Synaptosomal membrane proteins solubilized with 8% CHAPS-8 M urea were analyzed with two-dimensional electrophoresis (2DE). The membrane proteins were resolved up to 250 spots on a 2DE map, ranging in isoelectric points (pI) from 3.5 to 10.0 and molecular weights (MW) from 10 kDa to 200 kDa. Comparison of the mapped p...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00966203
更新日期:1990-05-01 00:00:00
abstract::Rett syndrome (RS) is an X-linked neurodevelopmental disorder mostly involving mutations in the gene for methyl-CpG-binding protein 2 (MECP2). Ganglioside abnormalities were previously found in cerebrum and cerebellum in RS patients. We evaluated total lipid distribution in cerebrum/brainstem, hippocampus, and cerebel...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-008-9874-7
更新日期:2009-06-01 00:00:00
abstract::The regional distribution of 2-amino-4-phosphonobutyrate (APB)/chloride-insensitive L-[3H]glutamate binding sites in the rat central nervous system was compared with that of APB/chloride-sensitive and with sodium-dependent binding sites. The distribution of APB-sensitive and APB-insensitive sites was not correlated, b...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00963986
更新日期:1984-03-01 00:00:00
abstract::This study attempted to investigate the possible involvement of the brain stem noradrenergic system in the development of hypertension in spontaneously hypertensive rats. Steady-state norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid concentrations and norepinephrine turnover were determined in the in...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00969761
更新日期:1989-01-01 00:00:00
abstract::The maintaining of homeostasis in the organism in response to a variable environment is provided by the highly hierarchic neuroendocrine-immune system. The crucial component of this system is the hypothalamus providing the endocrine regulation of key peripheral organs, and the adenohypophysis. In this case, neuron-der...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-010-0127-1
更新日期:2010-06-01 00:00:00
abstract::The specific precursors for neurotransmitter pools of glutamate giving rise to GABA in GABAergic neurons and nerve endings have not been clearly established. Glutamate is the immediate precursor for the production of GABA and it is suggested that ornithine (from arginine) might be serving as one of the precursors of g...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00964593
更新日期:1984-11-01 00:00:00
abstract::Any spinal cord injury carries the potential for persistent disability affecting motor, sensory and autonomic functions. To prevent this outcome, it is highly desirable to block a chain of deleterious reactions developing in the spinal areas immediately around the primary lesion. Thus, early timing of pharmacological ...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-017-2459-6
更新日期:2019-01-01 00:00:00
abstract::In the experimental setting, taurine is known to be released from swollen cells to reestablish their normal volume. However, its clinical relevance has not been fully understood. This study was undertaken to reveal changes in cerebrospinal fluid (CSF) amino acids concentration in patients with severe traumatic brain i...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-004-9693-4
更新日期:2005-01-01 00:00:00
abstract::Ecto-nucleotidases play a pivotal role in terminating the signalling via ATP and in producing adenosine, a neuromodulator in the nervous system. We have now investigated the pattern of adenosine formation with different concentrations of extracellular ATP in rat hippocampal nerve terminals. It was found that adenosine...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1012392719601
更新日期:2001-09-01 00:00:00
abstract::To evaluate the influence of light and darkness on brain pyroglutamyl-peptidase I (pGluPI) activity, four experimental groups of rats were compared at the same time-point (10.00 h). Two groups were designed with a standard 12-12 h light-dark cycle: In group A, the lights were on from 7.00 h to 19.00 h, and the experim...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1010996425408
更新日期:2001-05-01 00:00:00
abstract::We investigated the ability of hydrogen peroxide (H2O2) to cause apoptotic cell death in cultured rat forebrain neurons and the potential mechanisms by which oxidative stress triggers delayed neuronal death. H2O2 (25 microM for 5 min) reduced cell viability to 34.5 +/- 8.3% of untreated controls 20 h after exposure, a...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1022403224901
更新日期:1997-03-01 00:00:00
abstract::miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia-reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also in...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-020-02986-4
更新日期:2020-05-01 00:00:00
abstract::Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about...
journal_title:Neurochemical research
pub_type: 临床试验,杂志文章
doi:10.1007/BF00975048
更新日期:1993-12-01 00:00:00
abstract::The specific molecular events that underlie the age-related loss of cognitive function are poorly understood. Although not experimentally substantiated, age-dependent neuronal loss has long been considered central to age-related cognitive decline. More recently, age-related changes in brain white matter have taken pre...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-007-9341-x
更新日期:2007-12-01 00:00:00
abstract::Incubation of membranes derived from sarcotubular system of rabbit skeletal muscle with increasing concentrations of Triton X-100 produced both stimulation of the AChE activity and solubilization of this enzyme. Mild proteolytic treatment of microsomal membranes produced a several fold activation of the still membrane...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00969639
更新日期:1989-02-01 00:00:00
abstract::Reserpine evokes transsynaptic impulse activity by depleting catecholaminergic neurotransmitters in the rat brain. Previous studies suggest a relationship between catecholaminergic activity and calmodulin concentration. In this report we employ Northern blot analysis to examine the effect of a single subcutaneous inje...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF01474683
更新日期:1993-02-01 00:00:00
abstract::Hypoxia is one of the major common components of vascular risk factors for pathogenesis of Alzheimer's disease. This study investigated the possible relationship between hypoxia and alternative splicing of the excitatory amino acid transporter 2 (EAAT2) in a transgenic model for Alzheimer's disease. We used an APP23 m...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-007-9540-5
更新日期:2008-06-01 00:00:00
abstract::The Fatty Acid method was used to determine whether incorporation of plasma radiolabeled arachidonic acid into brain phospholipids is controlled by phospholipase A2. Awake rats received an i.v. injection of a phospholipase A2 inhibitor, manoalide (10 mg/kg), and then were infused i.v. with [1-(14)C]arachidonate or [3H...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1020788031720
更新日期:1998-10-01 00:00:00
abstract::The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems t...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00964358
更新日期:1978-02-01 00:00:00
abstract::In the present study, we investigated the effects of pioglitazone (PGZ) in the hippocampal CA1 region of low- or high-fat diet (LFD or HFD) fed gerbils after transient forebrain ischemia. After 8 weeks of LFD or HFD feeding, PGZ (30 mg/kg) was intraperitoneally administered to the gerbils, following which ischemia was...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-015-1568-3
更新日期:2015-05-01 00:00:00
abstract::The tyrosine phosphatase inhibitor BpV(phen) stimulated a concentration-dependent increase of phospholipase C (PLC) activity in bovine adrenal medullary chromaffin cells. This response was accompanied by an increase in PLCgamma1 tyrosine phosphorylation and its cytosketetal translocation. Insulin, at high concentratio...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/b:nere.0000042211.76499.c6
更新日期:2004-10-01 00:00:00
abstract::We examined the impact of peroxiredoxin-I (Prx-I) and peroxiredoxin-II (Prx-II) stable transduction on oxidative stress in PC12 neurons and NIH3T3 fibroblasts and found variability depending on cell type and Prx subtype. In PC12 neurons, Prx-II suppressed reactive oxygen species (ROS) generation by 36% (p < 0.01) rela...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1023/a:1026670620633
更新日期:2000-12-01 00:00:00
abstract::The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cho...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/BF00963926
更新日期:1983-02-01 00:00:00
abstract::Primary malignant brain cancer, one of the most deadly diseases, has a high rate of recurrence after treatment. Studies in the past several years have led to the hypothesis that the root of the recurrence may be brain tumor stem cells (BTSCs), stem-like subpopulation of cells that are responsible for propagating the t...
journal_title:Neurochemical research
pub_type: 杂志文章,评审
doi:10.1007/s11064-009-0079-5
更新日期:2009-12-01 00:00:00
abstract::We investigated the action of the new hypothalamic proline-rich peptide (PRP-1), normally produced by neurosecretory cells of hypothalamic nuclei (NPV and NSO), 3 and 4 weeks following rat sciatic nerve transection. The impulse activity flow of interneurons (IN) and motoneurons (MN) on stimulation of mixed (n. ischiad...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-005-2685-1
更新日期:2005-04-01 00:00:00
abstract::Oxidative stress is known to induce cell death in a wide variety of cell types, apparently by modulating intracellular signaling pathways. Activation of extracellular signal-regulated kinase (ERK) in oxidative stress remains controversial. In some cellular systems, the ERK activation is associated with protection agai...
journal_title:Neurochemical research
pub_type: 杂志文章
doi:10.1007/s11064-005-2449-y
更新日期:2005-02-01 00:00:00