Abstract:
:Mitochondria and releasable endoplasmic reticulum (ER) calcium modulate neuronal calcium signaling, and both change in Alzheimer's disease (AD). The releasable calcium stores in the ER are exaggerated in fibroblasts from AD patients and in multiple models of AD. The activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key mitochondrial enzyme complex, is diminished in brains from AD patients, and can be plausibly linked to plaques and tangles. Our previous studies in cell lines and mouse neurons demonstrate that reductions in KGDHC increase the ER releasable calcium stores. The goal of these studies was to test whether the relationship was true in human iPSC-derived neurons. Inhibition of KGDHC for one or 24 hr increased the ER releasable calcium store in human neurons by 69% and 144%, respectively. The effect was mitochondrial enzyme specific because inhibiting the pyruvate dehydrogenase complex, another key mitochondrial enzyme complex, diminished the ER releasable calcium stores. The link of KGDHC to ER releasable calcium stores was cell type specific as the interaction was not present in iPSC or neural stem cells. Thus, these studies in human neurons verify a link between KGDHC and releasable ER calcium stores, and support the use of human neurons to examine mechanisms and potential therapies for AD.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Chen H,Cross AC,Thakkar A,Xu H,Li A,Paull D,Noggle SA,Kruger L,Denton TT,Gibson GEdoi
10.1111/jnc.15160subject
Has Abstractpub_date
2020-08-31 00:00:00eissn
0022-3042issn
1471-4159pub_type
杂志文章abstract::Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by fro...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb03403.x
更新日期:1987-07-01 00:00:00
abstract::Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66062621.x
更新日期:1996-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2015-10-01 00:00:00
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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
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb01848.x
更新日期:1989-04-01 00:00:00
abstract::The role of the glutamate dehydrogenase reaction as a pathway of glutamate synthesis was studied by incubating synaptosomes with 5 mM 15NH4Cl and then utilizing gas chromatography-mass spectrometry to measure isotopic enrichment in glutamate and aspartate. The rate of formation of [15N]glutamate and [15N]aspartate fro...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb02110.x
更新日期:1991-07-01 00:00:00
abstract::As glucose hypometabolism in the brain is an early sign of Alzheimer´s dementia (AD), the diabetogenic drug streptozotocin (STZ) has been used to induce Alzheimer-like pathology in rat brain by intracereboventricular injection (icv-STZ). However, many details of the pathological mechanism of STZ in this AD model remai...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.15155
更新日期:2020-08-16 00:00:00
abstract::Platelet-activating factor (PAF) may be a neuromodulator involved in neural cell differentiation, cerebral inflammation, and ischemia. The PAF receptor is a member of the G protein-coupled receptor superfamily. In the present study, we sought to define the specific G protein(s) that mediate PAF-stimulated phosphoinosi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67041478.x
更新日期:1996-10-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04293.x
更新日期:2007-02-01 00:00:00
abstract::Muscarinic receptors mediate metabotropic actions of acetylcholine in the CNS and PNS and autocrine functions of acetylcholine in non-neuronal systems. Because of the lack of highly selective muscarinic ligands, the precise location, functional role, and roles in various diseases of the five muscarinic receptor subtyp...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2009.06092.x
更新日期:2009-06-01 00:00:00
abstract::The role of the serotonin (5-hydroxytryptamine) autoreceptor in the regulation of the activity of tryptophan hydroxylase was investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measuring the accumulation of 5-hydroxytryptophan in the presence of inhibition of aromatic L-amino acid...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1986.tb13063.x
更新日期:1986-03-01 00:00:00
abstract::The FE65 adaptor protein family was identified in two-hybrid screens as proteins that bind the cytoplasmic domain of the amyloid precursor protein (APP). Studies have shown that FE65 binding to APP modulates APP processing. Increased levels of alpha-secretase derived secreted APP (APPsalpha) and beta-amyloid (Abeta) w...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01009.x
更新日期:2002-08-01 00:00:00
abstract::Addiction is thought to be a memory process between perception and environmental cues and addicted patients often relapse when they come into contact with the drug-related context once again. Here, we used a conditioned place preference protocol to seek a more effective extinction methodology of methamphetamine (METH)...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13525
更新日期:2016-04-01 00:00:00
abstract::Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca(2+) influx into the pre-synaptic cytoplasm through voltage-dependent Ca(2+) channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12746
更新日期:2014-08-01 00:00:00
abstract::Silent information regulator 2, a member of NAD+-dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2005.03492.x
更新日期:2006-01-01 00:00:00
abstract::Substances that mimic the actions of causative gene products of familial Parkinson's disease (PD) are candidate as causative agents of idiopathic PD. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), an endogenous neurotoxin, is present at three times higher levels in CSF of PD patients than in CSF of control subjects...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06576.x
更新日期:2010-09-01 00:00:00
abstract::The hippocampal formation has been extensively research in terms of its putative neurotransmitters, anatomical connections, and behavioral relevance. An aspect of importance is the assessment of apparent neurotransmitter receptors by using receptor binding assays. In the present study, such assays were done in vitro t...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb06642.x
更新日期:1982-06-01 00:00:00
abstract::Intracerebroventricular injection of lipopolysaccharide (LPS) induces a marked increase in circulating interleukin (IL)-6 levels and in IL-6 mRNA expression in brain and peripheral organs. Recently, it was reported that intraperitoneal administration of alpha-adrenoceptor antagonists inhibits centrally injected LPS-in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1999.721625.x
更新日期:1999-04-01 00:00:00
abstract::The interaction of triethyltin (TET) and trimethyltin (TMT) with rat brain astrocytes in vitro was investigated. Both compounds are highly neurotoxic after in vivo application, cause neurobehavioral changes, and elicit neuronal and glial responses in the CNS. In this study, 5-week-old cultures were exposed to TMT or T...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.63062202.x
更新日期:1994-12-01 00:00:00
abstract::In brain, the precursor of imidazoleacetic acid (IAA), a GABAA agonist but a GABAC antagonist, is not known. In the periphery, IAA derives from oxidation of histamine. But in brain, histamine is thought to be metabolized solely by histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele-methylim...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68010142.x
更新日期:1997-01-01 00:00:00
abstract::We investigated the role of Ca(2+)-dependent protein kinases in the regulation of astrocytic cell volume. Calmodulin (CaM) antagonists were used to inhibit CaM and thus Ca2+/CaM-dependent protein kinase. The effect of these inhibitors as well as activators and inhibitors of protein kinase C (PKC) on astrocytic volume ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb10064.x
更新日期:1992-05-01 00:00:00
abstract::The carboxyl methylation of secretory proteins in vivo was investigated in bovine adrenal medullary cells in culture. Chromogranin A, the major intragranular secretory protein in adrenal medullary cells, and other secretory proteins were found to be carboxyl-methylated within secretory vesicles. The in vivo labeling p...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb03391.x
更新日期:1987-07-01 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::The effect of Gi/o protein-coupled receptors on adenylyl cyclase type 2 (AC2) has been studied in Sf9 insect cells. Stimulation of cells expressing AC2 with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) led to a twofold stimulation of cAMP synthesis that could be blocked with the protein kinase C inhib...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01270.x
更新日期:2002-12-01 00:00:00
abstract::Abstract The dualistic activities of the amyloid beta (Abeta) peptide as a pro-oxidant and ubiquitous constituent of amyloid deposits in Alzheimer's disease plaques and as an antioxidant of purported physiological function has been suggested but the mechanisms are far from being understood. In this report we measure s...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2004.02778.x
更新日期:2004-11-01 00:00:00
abstract::Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio-series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N-acetylgalactosaminyltransf...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64031274.x
更新日期:1995-03-01 00:00:00
abstract::Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) conjugation is markedly activated in the brain during deep to mode...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2012.07916.x
更新日期:2012-11-01 00:00:00
abstract::This study examined the hypothesis that chronic ethanol consumption results in significant abnormalities in both the dopaminergic and the serotonergic system of aged rats. Levels of dopamine (DA), serotonin [5-hydroxytryptamine (5-HT)], 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA)...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66052168.x
更新日期:1996-05-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control brain, suggestin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01103.x
更新日期:2002-09-01 00:00:00
abstract::Quinolinic acid (QUIN), an excitotoxic compound present in the mammalian CNS and periphery, has been hypothetically linked to human neurodegenerative disorders such as Huntington's disease and epilepsy. Quinolinic acid phosphoribosyltransferase (QPRT), the catabolic enzyme of QUIN, is found in the CNS and peripheral o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb05493.x
更新日期:1985-07-01 00:00:00