Abstract:
:Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFκB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFκB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFκB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 μM laquinimod, manHD monocytes released lower levels of IL-1β, IL-5, IL-8, IL-10, IL-13 and TNFα in response to stimulation. PreHD monocytes released lower levels of IL-8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFκB signalling in HD was assessed by inhibitor of kappa B (IκB) degradation kinetics, nuclear translocation of NFκB and interactions between IκB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFκB signalling in stimulated myeloid cell cultures from pre-manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFκB signalling. Read the Editorial Highlight for this article on page 670.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Dobson L,Träger U,Farmer R,Hayardeny L,Loupe P,Hayden MR,Tabrizi SJdoi
10.1111/jnc.13553subject
Has Abstractpub_date
2016-06-01 00:00:00pages
782-94issue
5eissn
0022-3042issn
1471-4159journal_volume
137pub_type
杂志文章abstract::[3H]Strychnine binding to rat pons + medulla membranes was used as a measure of glycine receptors or glycine receptor-coupled chloride channels in vitro. A series of compounds structurally related to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), which previously were shown to antagonize glycine responses in c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00667.x
更新日期:1986-09-01 00:00:00
abstract::We have recently isolated from bovine adrenal medulla a novel C-terminally amidated opioid peptide, amidorphin, which derives from proenkephalin A. Amidorphin revealed a widespread distribution in bovine, ovine, and porcine tissue. Particularly high concentrations of amidorphin immunoreactivity were detected in adrena...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb07218.x
更新日期:1985-11-01 00:00:00
abstract::Tanycytes are glial cells in the hypothalamus that are functionally part of the blood-brain barrier. They can sense nutrients and metabolites in the circulation such as glucose, then signal to neuronal systems to influence ingestive behaviour and energy storage, and ultimately affect body weight. The complex structure...
journal_title:Journal of neurochemistry
pub_type: 社论
doi:10.1111/jnc.15218
更新日期:2020-11-09 00:00:00
abstract::When synaptosomes from rat brain were incubated with S-adenosylmethionine (10(-3) M), noradrenaline uptake and KCl-stimulated release were decreased. These effects were dependent on MgCl2, temperature, and incubation time. We have investigated the enzymatic methylation of phosphatidylethanolamine to give phosphatidylc...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb06641.x
更新日期:1982-06-01 00:00:00
abstract::The ability of cholinergic vesicles to incorporate acetylcholine (ACh) was studied using highly purified synaptic vesicles from Torpedo electric organ. Depleted vesicles were capable of rapidly taking up exogenous ACh. Evidence that this represented true incorporation was that labelled ACh comigrated with vesicular AT...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1981.tb00479.x
更新日期:1981-08-01 00:00:00
abstract::Regulated intramembrane proteolysis (RIP) controls the communication between cells and the extracellular environment. RIP is essential in the nervous system, but also in other tissues. In the RIP process, a membrane protein typically undergoes two consecutive cleavages. The first one results in the shedding of its ect...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2011.07248.x
更新日期:2011-06-01 00:00:00
abstract::The cDNA for Tyr-Loc, a G protein-coupled receptor that clearly shows homology to a number of mammalian and fruit fly receptors for biogenic amines, was cloned from the nervous system of Locusta migratoria. Functional expression of the cloned cDNA was obtained in cultured insect cells, i.e., in Spodoptera SF9 cells us...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64062387.x
更新日期:1995-06-01 00:00:00
abstract::Thioltransferase (TTase) is a member of the family of thiol-disulfide oxidoreductases that are involved in the maintenance of sulfhydryl homeostasis in cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is the formation of protein-glutathione mixed dis...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0721170.x
更新日期:1999-03-01 00:00:00
abstract::Prothymosin alpha (ProTα), a nuclear protein devoid of signal sequence, has been shown to possess a number of cellular functions including cell survival. Most recently, we demonstrated that ProTα is localized in the nuclei of neurons, while it is found in both nuclei and cytoplasm in the astrocytes and microglia of ad...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2012.07897.x
更新日期:2012-10-01 00:00:00
abstract::The deficits in Alzheimer disease (AD) stem at least partly from neurotoxic beta-amyloid peptides generated from the amyloid precursor protein (APP). APP may also be cleaved intracellularly at Asp664 to yield a second neurotoxic peptide, C31. Previously, we showed that cleavage of APP at the C-terminus is required for...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.05031.x
更新日期:2008-02-01 00:00:00
abstract::Copper/zinc-superoxide dismutase (CuZn-SOD) transgenic mice overexpress the gene for human CuZn-SOD. To assess the effects of the overexpression of CuZn-SOD on the brain scavenging systems, we have measured the activities of manganese-SOD (Mn-SOD), catalase, and glutathione peroxidase (GSH-Px) in various regions of th...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb10051.x
更新日期:1992-05-01 00:00:00
abstract::Cyclic AMP phosphodiesterase activity in bovine brain coated vesicles displayed a Km of approximately 22 microM for cyclic AMP, a Vmax of 3.2 nmol/min/mg protein, and a Hill coefficient of 1.5, suggesting positive cooperativity. The enzyme activity was stimulated by cyclic GMP with maximal indexes of stimulation rangi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb00648.x
更新日期:1986-04-01 00:00:00
abstract::Several derivatives of conantokin-T (con-T), a naturally occurring, gamma-carboxyglutamate (Gla)-containing peptide with NMDA receptor (NMDAR) antagonist properties, were synthesized and evaluated for their ability to displace [(3)H]MK-801 from adult rat forebrain membranes. Analyses of progressive C-terminal truncati...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00281.x
更新日期:2001-05-01 00:00:00
abstract::Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable to free radicals, which can modulate protein tyrosine kinase (PTK) and phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases are as...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.03814.x
更新日期:2006-06-01 00:00:00
abstract::N-Copine is a novel protein with two C2 domains. Its expression is brain specific and up-regulated by neuronal activity such as kainate stimulation and tetanus stimulation evoking hippocampal CA1 long-term potentiation. We examined the localization and subcellular distribution of N-copine in mouse brain. In situ hybri...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.0720373.x
更新日期:1999-01-01 00:00:00
abstract::cis-4-Aminocrotonic acid (CACA; 100 microM), an analogue of GABA in a folded conformation, stimulated the passive release of [3H] GABA from slices of rat cerebellum, cerebral cortex, retina, and spinal cord and of beta-[3H]alanine from slices of cerebellum and spinal cord without influencing potassium-evoked release. ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68020786.x
更新日期:1997-02-01 00:00:00
abstract::The nuclear factor 1 (NF-1) motifs, NF-1 II/III, In the two 98-bp repeats of the transcription-regulatory region of JC virus (JCV), have a critical role in brain-specific transcription from the JCV early promoter-enhancer. In this study, the role of these motifs in transactivation of the JCV late promoter-enhancer (JC...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67020473.x
更新日期:1996-08-01 00:00:00
abstract::Brain edema in hepatic encephalopathy has been associated with circulating ammonia that is metabolized to glutamine. We measured alterations in blood chemistry and brain regional specific gravity and ion and amino acid contents in models of simple hyperammonemia and liver failure induced by daily administrations of am...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62010197.x
更新日期:1994-01-01 00:00:00
abstract::We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intrav...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0752392.x
更新日期:2000-12-01 00:00:00
abstract::The incorporation of radioactive phosphate into proteins of both normal and regenerating ganglia of the sympathetic nervous system of the rat is reported. The incorporation reactions were carried out in vitro by incubating homogenates of excised ganglia with [gamma-32P]ATP under various conditions. It was found that i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07247.x
更新日期:1989-06-01 00:00:00
abstract::Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06876.x
更新日期:2010-09-01 00:00:00
abstract::Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13347
更新日期:2015-12-01 00:00:00
abstract::Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb02329.x
更新日期:1990-03-01 00:00:00
abstract::Kainate receptors (KARs) have been described as modulators of synaptic transmission at different synapses. However, this role of KARs has not been well characterized in the amygdala. We have explored the effect of kainate receptor activation at the synapse established between fibers originating at medial geniculate nu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2012.07665.x
更新日期:2012-04-01 00:00:00
abstract::Three serine residues (Ser193, Ser194, Ser197) in the fifth transmembrane-spanning region of the D2 dopamine receptor have been mutated separately to alanine and the effects of the mutations determined in ligand-binding experiments with [3H] spiperone. For many antagonists the mutations had little effect, showing that...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66010394.x
更新日期:1996-01-01 00:00:00
abstract::Animals trained in a passive avoidance task exhibit a transient time-dependent increase in hippocampal neural cell adhesion molecule (NCAM) polysialylation at 12-24 h following the initial learning trial. Using immunocytochemical techniques with a monoclonal antibody that specifically recognises NCAM-polysialic acid h...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65062796.x
更新日期:1995-12-01 00:00:00
abstract::An early biochemical change in the Parkinsonian substantia nigra (SN) is reduction in total glutathione (GSH + GSSG) levels in affected dopaminergic neurons prior to depletion in mitochondrial complex I activity, dopamine loss, and cell death. We have demonstrated using dopaminergic PC12 cell lines genetically enginee...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02929.x
更新日期:2005-03-01 00:00:00
abstract::The Review highlighted in this Editorial followed a CAEN Return Home Grant. ...
journal_title:Journal of neurochemistry
pub_type: 评论,社论
doi:10.1111/jnc.14115
更新日期:2017-10-01 00:00:00
abstract::The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [3H]acetylcholine ([3H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A1/A2 agonist 2-chloroadenosine (CADO; 2-10 microM) inhibited, in a concentration...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63010207.x
更新日期:1994-07-01 00:00:00
abstract::A loss of balance between excitatory and inhibitory signaling leads to excitoxicity, and contributes to ischemic cell death. Reduced synaptic inhibition as a result of dysfunction of the ionotropic GABAA receptor has been suggested as one of the major causes for this imbalance, although the underlying mechanisms remai...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02841.x
更新日期:2005-01-01 00:00:00