Abstract：
:Nigrostriatal neurodegeneration in Parkinson's disease (PD) has been postulated to be caused by various pathological conditions, such as mitochondrial defects, oxidative stress, and ubiquitin-proteasome system (UPS) dysfunction. Pharmacological strategies designed to interfere with these pathological pathways may effectively counteract the degeneration. Rasagiline and selegiline are selective and irreversible monoamine oxidase-B inhibitors that possess significant protective properties on dopamine neurons in various pre-clinical models of PD. In the present study, the neuroprotective and neurorestorative effects of rasagiline and selegiline were compared in an animal model of PD produced by inhibition of the UPS. C57BL/6 male mice were microinjected bilaterally with UPS inhibitor lactacystin (1.25 mug/side), into the medial forebrain bundle. Administration of rasagiline (0.2 mg/kg, i.p. once per day) or selegiline (1 mg/kg, i.p. once per day), started 7 days before or after (up to 28 days) after lactacystin microinjection. We found that both rasagiline and selegiline exerted a significant neuroprotective effect against lactacystin-induced neurodegeneration; but only rasagiline managed to restore the nigrostriatal degeneration. Furthermore, rasagiline showed a modest protection against lactacystin-induced inhibition of proteasomal activity. Our study indicates that compared with selegiline, rasagiline is more potent in protecting neurodegeneration induced by UPS impairment and may, therefore, exert disease-modifying effects in PD.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Zhu W,Xie W,Pan T,Jankovic J,Li J,Youdim MB,Le Wdoi
10.1111/j.1471-4159.2008.05330.xsubject
Has Abstractpub_date
2008-06-01 00:00:00pages
1970-8issue
5eissn
0022-3042issn
1471-4159pii
JNC5330journal_volume
105pub_type
杂志文章abstract：:We have proposed that a very early step in the pathogenesis of idiopathic Parkinson's disease is the elevated translocation of L-cysteine into neuromelanin-pigmented dopaminergic neurons in the substantia nigra. This influx of L-cysteine was proposed to divert the normal neuromelanin pathway by scavenging dopamine-o-q...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71052049.x
更新日期：1998-11-01 00:00:00
abstract：:Voltage-gated sodium channels (VGSC) are involved in the generation of action potentials in neurons. Brevetoxins (PbTx) are potent allosteric enhancers of VGSC function and are associated with the periodic 'red tide' blooms. Using PbTx-2 as a probe, we have characterized the effects of activation of VGSC on Ca(2+) dyn...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02407.x
更新日期：2004-05-01 00:00:00
abstract：:The biotransformation of the opioid peptide dynorphin A(1-17) was investigated in striatum of freely moving Fischer rats, by direct infusion of this peptide, followed by recovery of the resulting biotransformation products via microdialysis and identification using matrix-assisted laser desorption/ionization mass spec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01859.x
更新日期：2003-08-01 00:00:00
abstract：:Brain homogenate, cerebral microvessels, and endothelial cells (ECs) were prepared from 15-18-week-old human fetuses and analyzed biochemically for the presence of elements of the cholinergic system [acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and butyrylcholinesterase]. The ECs were cultured, and t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb03478.x
更新日期：1991-06-01 00:00:00
abstract：:Currently, the underlying mechanisms and the specific cell types associated with Japanese encephalitis-associated leukocyte trafficking are not understood. Brain microvascular endothelial cells represent a functional barrier and could play key roles in leukocyte central nervous system trafficking. We found that cultur...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2012.07889.x
更新日期：2012-10-01 00:00:00
abstract：:Exposure to cocaine-associated conditioned stimuli elicits craving and increases the probability of cocaine relapse in cocaine users even after extended periods of abstinence. Recent evidence indicates that cocaine seeking can be inhibited by disrupting the reconsolidation of the cocaine cue memories and that basolate...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07277.x
更新日期：2011-07-01 00:00:00
abstract：:Declining levels of estrogen in women result in increases in gonadotropins such as luteinizing hormone (LH) through loss of feedback inhibition. LH, like estrogen, is modulated by hormone replacement therapy. However, the role of post-menopausal gonadotropin increases on cognition has not been evaluated. Here, we demo...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06502.x
更新日期：2010-02-01 00:00:00
abstract：:2'-Deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase (ADA), is increasingly used as a tool to investigate adenosine metabolism and neuromodulation. To advance further the usefulness of DCF for studies of purines in the CNS, we determined the inhibitory potency of this compound against ADA and adenylate ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb01945.x
更新日期：1990-04-01 00:00:00
abstract：:The critical hyaluronan binding motif (HABM) in sialoprotein associated with cones and rods (SPACR) has already been determined. As sialoproteoglycan associated with cones and rods, another interphotoreceptor matrix molecule, binds to chondroitin sulfate and heparin with or without the employment of HABMs, respectivel...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05669.x
更新日期：2008-11-01 00:00:00
abstract：:The behavioral and functional significance of the extrasynaptic inhibitory GABA(A) receptors in the brain is still poorly known. We used a transgenic mouse line expressing the GABA(A) receptor alpha6 subunit gene in the forebrain under the Thy-1.2 promoter (Thy1alpha6) mice ectopically expressing alpha6 subunits espec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.05136.x
更新日期：2008-04-01 00:00:00
abstract：:The changes in activity of phospholipid methyltransferase I and [3H]S-adenosyl-L-homocysteine ([3H]SAH) binding were determined in cortical membrane preparations from newborn rats and rats 1, 2, and 8 months old. The activity of phospholipid methyltransferase I and the [3H]SAH binding were significantly greater (respe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb05470.x
更新日期：1985-07-01 00:00:00
abstract：:Although 3,4-dihydroxyphenylethylamine (dopamine, DA) and vasoactive intestinal peptide (VIP) have been reported to stimulate adenylate cyclase activity in the rabbit retina, possible interactions between VIP-sensitive and DA-sensitive adenylate cyclase systems have not been previously investigated. To elucidate the i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb12955.x
更新日期：1986-01-01 00:00:00
abstract：:NMDA (N-methyl-D-aspartate) subtype of glutamate receptors are core components of dendritic spine postsynaptic densities (PSDs), in which they are anchored via their carboxy-terminal tails to cytoskeletal proteins. In this study, we examined the role of the neuronal intermediate filament protein, neurofilament-light (...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02936.x
更新日期：2005-02-01 00:00:00
abstract：:Ischemic stress in the brain induces acute and massive neuronal death in the targeted area, which is followed by a second round of detrimental processes, called delayed neuronal death, in the neighboring areas. To test the hypothesis that transcriptional control plays a role in the pathophysiology of the postischemic ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02429.x
更新日期：2004-06-01 00:00:00
abstract：:Microtubule-associated proteins (MAPs) were phosphorylated by a Ca2+- and calmodulin-dependent protein kinase from rat brain cytosol. The maximal amount of phosphate incorporated into MAPs was 25 nmol of phosphate/mg protein. A Ka value of the enzyme for calmodulin was 57.0 nM, with MAPs as substrates. Among MAPs, MAP...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb09060.x
更新日期：1983-10-01 00:00:00
abstract：:We report that a subtoxic dose of the succinate dehydrogenase (SDH) inhibitor malonate greatly enhances the neurotoxicity of three different excitatory amino acid agonists: N-methyl-D-aspartate (NMDA), S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA), and L-glutamate. In male Sprague-Dawley rats, in...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64052332.x
更新日期：1995-05-01 00:00:00
abstract：:Studies performed over the past several years have provided evidence that phosphorylation of proteins is important in the regulation of neurotransmitter release. In this study, it is shown that rabphilin-3A is present in cerebellar granule cells as a phosphoprotein, by using 32P-labeling of cerebellar granule cells, i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71041661.x
更新日期：1998-10-01 00:00:00
abstract：:S-100 proteins are a group of three 21-kilodalton, acidic, Ca2+-binding proteins of the "E-F hand" type shown to regulate several cell activities, including microtubule (MT) assembly-disassembly. We show here that S-100 proteins interact with MTs assembled from either whole microtubule protein or purified tubulin, bot...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb01841.x
更新日期：1989-04-01 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：: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：:Vitamin A metabolite retinoic acid (RA) plays a major role in the aging adult brain plasticity. Conversely, chronic excess of glucocorticoids (GC) elicits some deleterious effects in the hippocampus. We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons. We investi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12192
更新日期：2013-05-01 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：:Pigment epithelium-derived factor (PEDF), purified from human fetal retinal pigment epithelium cell culture medium, was shown to potentiate the differentiation of human Y-79 retinoblastoma cells. To investigate potential neurotrophic effects of PEDF on neurons other than those of retinal derivation, we used cultures o...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64062509.x
更新日期：1995-06-01 00:00:00
abstract：:The NMDA receptor/channel has been shown to be inhibited by ethanol in the clinically relevant range 25-100 mM. We studied heteromeric assemblies (NR1b/NR2) of the NMDA receptor, expressed in oocytes, to address three questions regarding this inhibition, and discovered the following: (1) The inhibition was nearly equi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65010140.x
更新日期：1995-07-01 00:00:00
abstract：:Poly(ADP-ribose) polymerase associated with free cytoplasmic messenger ribonucleoprotein particles (free mRNP particles) carrying messenger RNA has been characterized in rat brain. There were first-order kinetics for NAD with an apparent Km for NAD of 90.5 +/- 0.70 microM and Vmax of 19.7 +/- 2.8 pmol ADP-ribose incor...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb01075.x
更新日期：1988-08-01 00:00:00
abstract：:Dopamine beta-hydroxylase (DBH; EC 1.14.17.1) exists as membrane-bound and soluble forms in neurosecretory vesicles. The features of DBH required for glycosylation and incorporation into membranes were studied in a cell-free system. Translation of full-length DBH with microsomal membranes generated two glycosylated pr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64010025.x
更新日期：1995-01-01 00:00:00
abstract：:Matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry is used to examine the formation of N-pyroglutamate (pGlu) in single, identified neurons from Aplysia. Six pGlu peptides are identified in the R3-14 and the R15 neurons that result from in vivo processing of peptides containing either Gl...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0720676.x
更新日期：1999-02-01 00:00:00
abstract：:Calcium/calmodulin-dependent kinase II (CaMKII) facilitates L-type calcium channel (LTCC) activity physiologically, but may exacerbate LTCC-dependent pathophysiology. We previously showed that CaMKII forms stable complexes with voltage-gated calcium channel (VGCC) beta(1b) or beta(2a) subunits, but not with the beta(3...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06436.x
更新日期：2010-01-01 00:00:00
abstract：:The biosynthesis of angiotensin II-like peptide was measured in primary cultured brain cells from the fetal rat. Cells from the whole brains of 20-day gestational age Sprague-Dawley rats were dissociated by mild trypsinization and grown for 5 days in supplemented (serum-free) medium prior to experimental analysis. The...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12791.x
更新日期：1984-09-01 00:00:00
abstract：:Isolated rat CNS mitochondria and cultured cortical astrocytes were examined for behavior indicative of a mitochondrial permeability transition (mPT). Exposure of isolated CNS mitochondria to elevated calcium or phosphate or both produced loss of absorbance indicative of mitochondrial swelling. The absorbance decrease...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69020524.x
更新日期：1997-08-01 00:00:00
