Abstract：
:Lewy body disease (LBD) development is enhanced by mutations in the GBA gene coding for glucocerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to evaluate if lysosomal changes contribute to the pathogenesis of idiopathic LBD. Analysis of post-mortem frontal cortex tissue from 7 GBA mutation carriers with LBD, 5 GBA mutation carriers with no signs of neurological disease and human neural stem cells exposed to a GCase inhibitor was used to determine how GBA mutation contributes to LBD. GBA mutation carriers demonstrated a significantly reduced level of GCase protein and enzyme activity and retention of glucocerebrosidase isoforms within the endoplasmic reticulum (ER). This was associated with enhanced expression of the lysosomal markers LAMP1 and LAMP2, though the expression of ATP13A2 and Cathepsin D was reduced, along with the decreased activity of Cathepsin D. The ER unfolded protein response (UPR) regulator BiP/GRP78 was reduced by GBA mutation and this was a general phenomenon in LBD. Despite elevation of GRP94 in LBD, individuals with GBA mutations showed reduced GRP94 expression, suggesting an inadequate UPR. Finally, human neural stem cell cultures showed that inhibition of GCase causes acute reduction of BiP, indicating that the UPR is affected by reduced glucocerebrosidase activity. The results indicate that mutation in GBA leads to additional lysosomal abnormalities, enhanced by an impaired UPR, potentially causing α-synuclein accumulation.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Kurzawa-Akanbi M,Hanson PS,Blain PG,Lett DJ,McKeith IG,Chinnery PF,Morris CMdoi
10.1111/j.1471-4159.2012.07879.xsubject
Has Abstractpub_date
2012-10-01 00:00:00pages
298-309issue
2eissn
0022-3042issn
1471-4159journal_volume
123pub_type
杂志文章abstract：:Repeated intermittent treatment with amphetamine (AMPH) induces both neurite outgrowth and enhanced AMPH-stimulated dopamine (DA) release in PC12 cells. We investigated the role of protein kinases in the induction of these AMPH-mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein ki...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02127.x
更新日期：2003-12-01 00:00:00
abstract：:Androgens affect cognitive processes in both humans and animals. The effects of androgens may be limited to certain cognitive domains, specifically spatial memory, but this hypothesis remains elusive. Here, we tested castrated and sham-operated mice in various behavioral tasks to ask whether androgens affect multiple ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06183.x
更新日期：2009-08-01 00:00:00
abstract：:Most recent studies aimed at defining the cellular and molecular mechanisms of Pavlovian fear conditioning have focused on protein kinase signaling pathways and the transcription factor cAMP-response element binding protein (CREB) that promote fear memory consolidation in the lateral nucleus of the amygdala (LA). Desp...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06491.x
更新日期：2010-02-01 00:00:00
abstract：:Tetanus neurotoxin and botulinum neurotoxins are the causative agents of tetanus and botulism. They block the release of neurotransmitters from synaptic vesicles in susceptible animals and man and act in nanogram quantities because of their ability to specifically attack motoneurons. They developed an ingenious strate...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2009.06093.x
更新日期：2009-06-01 00:00:00
abstract：:Previous studies have demonstrated opposing roles for adenosine A1 and A2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor-activating doses of the A2A receptor antagonist MSX-3 significantly decreased extracellu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02245.x
更新日期：2004-03-01 00:00:00
abstract：:Alzheimer's disease (AD) is a neurodegenerative pathology characterized by aggregates of amyloid-β (Aβ) and phosphorylated tau protein, synaptic dysfunction, and spatial memory impairment. The Wnt signaling pathway has several key functions in the adult brain and has been associated with AD, mainly as a neuroprotectiv...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14278
更新日期：2018-02-01 00:00:00
abstract：:Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to ischemic brain injury via complex pathophysiological events, including excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+, and reactive oxygen species (ROS) generation. Each of these could also contribute to cerebral edema...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01772.x
更新日期：2003-06-01 00:00:00
abstract：:Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12352
更新日期：2013-09-01 00:00:00
abstract：:Differential assembly of N-methyl-D-aspartate (NMDA) receptor subunits determines their functional characteristics. Using in situ hybridization, we found a selective increase of the subunits NR1 and NR2A mRNA at 24 h in ventral motor neurons (VMN) caudal to a standardized spinal cord contusion injury (SCI). Other neur...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0750174.x
更新日期：2000-07-01 00:00:00
abstract：:There is great interest in soy isoflavones as alternatives to endogenous estrogens not only in hormonal pathologies, but also in inflammatory, neurodegenerative diseases, and pain. We investigated the effect of the isoflavone genistein on neuropathic pain. Genistein binds estrogen receptors (ER) with higher affinity f...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05614.x
更新日期：2008-10-01 00:00:00
abstract：:This Editorial highlights a study by Baglietto-Vargas et al. 2015 published in this issue of J. Neurochem. Stress is one of the environmental factors that can contribute to Alzheimer's disease pathogenesis. However, the role of modern-life stress has not been investigated yet. The authors reveal that modern-life stres...
journal_title：Journal of neurochemistry
pub_type： 评论,社论
doi：10.1111/jnc.13210
更新日期：2015-09-01 00:00:00
abstract：:The metabolism and blood-brain transport of choline (Ch) were investigated in perfused canine brain under control conditions and for 60 min after inhibition of brain cholinesterases by the organophosphorus (OP) compounds soman (pinacolylmethylphosphonofluoridate). Ch and acetylcholine (ACh) in blood and brain samples ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb02993.x
更新日期：1988-03-01 00:00:00
abstract：:The Ret receptor tyrosine kinase is the common signaling receptor for the glial cell line-derived neurotrophic factor (GDNF) family ligands. The Met918Thr mutation leads to constitutive activation of Ret and is responsible for dominantly inherited cancer syndrome MEN2B. Previously, we found that the mice carrying the ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05265.x
更新日期：2008-06-01 00:00:00
abstract：:The expression of Nex1 peaks during brain development when neurite outgrowth and synaptogenesis are highly active. We previously showed that Nex1 is a critical effector of the nerve growth factor (NGF) pathway and its overexpression results in spontaneous neuritogenesis. Furthermore, the PC12-Nex1 cells exhibit accele...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02814.x
更新日期：2004-12-01 00:00:00
abstract：:Pro-thyrotropin-releasing hormone (proTRH) is the precursor to thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2), the hypothalamic releasing factor that stimulates synthesis and release of thyrotropin from the pituitary gland. Five copies of the TRH progenitor sequence (Gln-His-Pro-Gly) and seven cryptic peptides ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65062462.x
更新日期：1995-12-01 00:00:00
abstract：:The ubiquitous second messenger cyclic GMP (cGMP) is synthesized by soluble guanylate cyclases in response to nitric oxide (NO) and degraded by phosphodiesterases (PDE). We studied the homeostasis of cGMP in living thalamic neurons by using the genetically encoded fluorescence resonance energy transfer sensor Cygnet, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04657.x
更新日期：2007-09-01 00:00:00
abstract：:The time course of changes in extracellular glutamic acid levels and their Ca2+ dependency were studied in the rat striatum during focal cerebral ischaemia, using microdialysis. Ischaemia-induced changes were compared with those produced by high K(+)-evoked local depolarization. To optimize time resolution, glutamate ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63031003.x
更新日期：1994-09-01 00:00:00
abstract：:The objective of the present study was to assess metabolic changes in the neocortex and hippocampus of well-oxygenated or moderately hypoxic rats in which fluorothyl-induced seizures were sustained for 5 or 20 min, or which were allowed recovery periods of 5, 15, or 45 min following cessation of 20-min seizure activit...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb08778.x
更新日期：1985-05-01 00:00:00
abstract：:The presence of gamma-hydroxybutyric acid (GHB) in synaptosome-enriched fractions of rat brain was ascertained using a GLC technique. The stability of GHB in synaptosomes was evaluated by addition of various gamma-aminobutyric acid (GABA) transaminase (GABA-T) inhibitors, GHB, or ethosuximide to the homogenizing mediu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb13147.x
更新日期：1987-01-01 00:00:00
abstract：:We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isol...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb03463.x
更新日期：1991-06-01 00:00:00
abstract：:Previous studies showed that prolonged access to cocaine or heroin self-administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacok...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01833.x
更新日期：2003-07-01 00:00:00
abstract：:Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of the blood-brain barri...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0731461.x
更新日期：1999-10-01 00:00:00
abstract：:A mitochondrial fraction, purified from pig brain, was found to contain associated polypeptides with the same electrophoretic migration and isoelectric points as the alpha- and beta-tubulin subunits present in brain microtubules. When analyzed by Western blotting these polypeptides reacted specifically with purified t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb04015.x
更新日期：1985-08-01 00:00:00
abstract：:Research on stem cells has developed as one of the most promising areas of neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was indisputably accepted, eliciting great research efforts. Neural stem cells in the adult mammalian brain are located in the 'neurogenic' areas of the subventricular...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.12084
更新日期：2013-01-01 00:00:00
abstract：:Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine-rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13612
更新日期：2016-06-01 00:00:00
abstract：:Previous studies have indicated that the brains of DBA/2J (D2) mice have a more heavily myelinated CNS than those of C57BL/6J (B6) at postnatal days 17-21. However, the amount of myelin in the brains of F1 (B6 X D2) hybrids is even higher than in their parental strains. To investigate further factors involved in regul...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb09995.x
更新日期：1987-10-01 00:00:00
abstract：:The protein kinases and protein phosphatases that act on tyrosine hydroxylase in vivo have not been established. Bovine adrenal chromaffin cells were permeabilized with digitonin and incubated with [gamma-32P]ATP, in the presence or absence of 10 microM Ca2+, 1 microM cyclic AMP, 1 microM phorbol dibutyrate, or variou...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69062387.x
更新日期：1997-12-01 00:00:00
abstract：:The presynaptic terminals of skate (Raja montagui) electric organ were tested for their sensitivity to calcium channel antagonists. Acetylcholine (ACh) release and the elevation of intraterminal Ca2+ concentrations triggered by K+ depolarisation were studied. ACh release was measured as 3H efflux from slices of organ ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64020944.x
更新日期：1995-02-01 00:00:00
abstract：:Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13987
更新日期：2017-05-01 00:00:00
abstract：:It is necessary for the cell-cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell-cycle-related proteins contribute to the process. p27...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13918
更新日期：2017-02-01 00:00:00
