Abstract：
:Null mutations in progranulin (GRN) are associated with frontotemporal lobar degeneration characterized by intraneuronal accumulation of TAR DNA-binding protein-43 (TDP-43). However, the mechanism by which GRN deficiency leads to neurodegeneration remains largely unknown. In primary cortical neurons derived from Grn knockout (Grn(-/-) ) mice, we found that Grn-deficiency causes significantly reduced neuronal survival and increased caspase-mediated apoptosis, which was not observed in primary mouse embryonic fibroblasts derived from Grn(-/-) mice. Also, neurons derived from Grn(-/-) mice showed an increased amount of pTDP-43 accumulations. Furthermore, proteasomal inhibition with MG132 caused increased caspase-mediated TDP-43 fragmentation and accumulation of detergent-insoluble 35- and 25-kDa C-terminal fragments in Grn(-/-) neurons and mouse embryonic fibroblasts. Interestingly, full-length TDP-43 also accumulated in the detergent-insoluble fraction, and caspase-inhibition prevented MG132-induced generation of TDP-43 C-terminal fragments but did not block the pathological conversion of full-length TDP-43 from soluble to insoluble species. These data suggest that GRN functions as a survival factor for cortical neurons and GRN-deficiency causes increased susceptibility to cellular stress. This leads to increased aggregation and accumulation of full-length TDP-43 along with its C-terminal derivatives by both caspase-dependent and independent mechanisms.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Kleinberger G,Wils H,Ponsaerts P,Joris G,Timmermans JP,Van Broeckhoven C,Kumar-Singh Sdoi
10.1111/j.1471-4159.2010.06961.xsubject
Has Abstractpub_date
2010-11-01 00:00:00pages
735-47issue
3eissn
0022-3042issn
1471-4159pii
JNC6961journal_volume
115pub_type
杂志文章abstract：:A glycoprotein ATPase in cholinergic synaptic vesicles of Torpedo electric organ was solubilized with octa-ethylene glycol dodecyl ether detergent. Study of potential stabilizing factors identified crude brain phosphatidylserine, glycerol, dithiothreitol, and protease inhibitors as of value in maintaining activity. Th...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb08524.x
更新日期：1989-11-01 00:00:00
abstract：:Effective drugs are not available to protect against beta-amyloid peptide (A beta)-induced neurotoxicity. Cortical neurons from rat embryos were treated with the toxic fragment A beta25-35 at 1 microM in the presence or absence of flupirtine, a triaminopyridine, successfully applied clinically as a nonopiate analgesic...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.68062371.x
更新日期：1997-06-01 00:00:00
abstract：:The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 mi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.740684.x
更新日期：2000-02-01 00:00:00
abstract：:In frozen-thawed repeatedly washed rat cortical synaptic membranes, Ca2+ (1-5 mM) decreased the binding of [3H]muscimol whereas it increased the binding of [3H]gamma-aminobutyric acid (GABA). However, the binding of [3H]GABA was decreased by the same extent as the binding of [3H]muscimol when the membranes were incuba...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb11840.x
更新日期：1983-07-01 00:00:00
abstract：:The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K+ that precedes massive cell depolarization, and rapid downhill fluxes of K+, Na+, Cl-, and Ca2+. As it has been speculated that a ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb04957.x
更新日期：1990-11-01 00:00:00
abstract：:Prolonged hypoxia exerts profound effects on cell function, and has been associated with increased production of amyloid beta peptides (A beta Ps) of Alzheimer's disease. Here, we have investigated the effects of chronic hypoxia (2.5% O2, 24 h) on capacitative Ca2+ entry (CCE) in primary cultures of rat type-I cortica...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01785.x
更新日期：2003-06-01 00:00:00
abstract：:Endocannabinoids (eCBs) play key roles in short-term and long-term synaptic plasticity in the corticostriatal circuit. By activating cannabinoid receptors expressed in the central nervous system, eCBs regulate several neural functions and behaviors. The major eCB 2-arachidonoyl-glycerol (2-AG) is particularly importan...
journal_title：Journal of neurochemistry
pub_type： 社论
doi：10.1111/jnc.14977
更新日期：2020-05-01 00:00:00
abstract：:Aggregation of conformation-abnormal peptides probably plays a key role in the pathogenesis of many neurodegenerative diseases. DSCR1 Down syndrome (DS) critical region 1, was identified from a chromosomal region (21q22.1-q22.2) for the clinical manifestations of DS when an extra-copy is present. We report that expres...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02294.x
更新日期：2004-03-01 00:00:00
abstract：:The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02792.x
更新日期：1984-05-01 00:00:00
abstract：:The Cys-loop receptor family consists of nicotinic acetylcholine receptors (nAChR), glycine receptor, GABA-A and some other receptors. They fulfill a plethora of functions, whereas their malfunctioning is associated with many diseases. All three domains - extracellular ligand-binding, membrane and cytoplasmic - of the...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2010.07060.x
更新日期：2011-03-01 00:00:00
abstract：:Our previous work demonstrated that immunoproteasome is up-regulated in the retina and brain in response to injury that does not involve an inflammatory response (J. Neurochem. 2008; 106:158). These results suggest additional non-immune functions for the immunoproteasome in the cellular stress response pathway. The pr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06688.x
更新日期：2010-06-01 00:00:00
abstract：:A neurochemical evaluation of beagle dogs with naturally occurring spontaneous generalized convulsive seizures was performed. Amino acid profiles of serum, cerebrospinal fluid (CSF), and biopsied cerebral cortex from epileptic dogs were compared with those from seizure-free siblings. No differences in absolute levels ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb07862.x
更新日期：1980-11-01 00:00:00
abstract：:Primary cultures of astrocytes from newborn rat brain showed evidence of a substrate-saturable process for glucose transport. The system shows a relatively high affinity for the substrate, with an apparent Km of approximately 1 mM. Maintenance of the cells in medium containing thyroid-hormone-free serum for 3, 6, or 9...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb07239.x
更新日期：1985-11-01 00:00:00
abstract：:Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 6 of the gene is an alternatively spliced cassette whose expression pattern and splicing regulation had not been previously analyzed in the human. The expression profile of exon 6 is comp...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70041346.x
更新日期：1998-04-01 00:00:00
abstract：:Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short-lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quan...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64041819.x
更新日期：1995-04-01 00:00:00
abstract：:beta-Adrenergic receptor subtypes, beta 1 and beta 2, were studied during pre- and postnatal development in the rat brain. [125I]Iodocyanopindolol (6-300 pmol/L) binding assays in the presence of 5-hydroxytryptamine (0.6-6 mumol/L) were used to measure exclusively beta-adrenergic receptors. In forebrain tissue, satura...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb08235.x
更新日期：1991-09-01 00:00:00
abstract：:Imprinting in chicks is a form of juvenile learning that has been used to study the basic cellular mechanisms of learning and memory. The forebrain area mediorostral neostriatum/hyperstriatum ventrale (MNH) is a center for acoustic imprinting. Electrophysiological and pharmacological behavioral studies in the MNH have...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66031167.x
更新日期：1996-03-01 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：:In the human fetus, obtained postmortem at estimated gestational ages of 8-22 weeks, biochemical activities of cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were comparable to those of adult brain tissue. In contrast cholinergic receptor binding, including muscarinic M1 and M2 subtypes (mea...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1986.tb00749.x
更新日期：1986-10-01 00:00:00
abstract：:This study focuses on the potential involvement of carnitine palmitoyltransferase (CPT) on the phospholipid and triglyceride fatty acid turnover in neurons. This category of enzymes, which has been identified in several rat brain tissues, is well known for its role in modulating cellular fatty acid oxidation. Neuronal...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62041530.x
更新日期：1994-04-01 00:00:00
abstract：:We have screened a human cDNA library using an expressed sequence tag related to the BM-40/secreted protein, acidic and rich in cysteine (SPARC)/osteonectin family of proteins and isolated a novel cDNA. It encodes a protein precursor of 424 amino acids that consists of a signal peptide, a follistatin-like domain, a Ca...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0730012.x
更新日期：1999-07-01 00:00:00
abstract：:A simple and rapid method for preparation of enriched neurofilament protein from mammalian peripheral nerve or spinal cord is described. Tissue extracts from guinea pig nerve or spinal cord are fractionated by ammonium sulfate fractionation, chromatography on Sepharofe 4B, and precipitation with ethanol. Molecular exc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb09007.x
更新日期：1980-12-01 00:00:00
abstract：:Methods are described for the determination of sheep spinal cord tissue fluid content and norepinephrine, serotonin, and dopamine concentrations after experimental injury. The amount of tissue fluid varied in different regions of sheep spinal cord following injury. Norepinephrine and serotonin wet weight concentration...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb07074.x
更新日期：1980-10-01 00:00:00
abstract：:NNC 01-0012, a second-generation benzazepine compound, pharmacologically differentiates multiple vertebrate D1 receptor subtypes (D1A, D1B, D1C, and D1D) and displays high selectivity and affinity for dopamine D1C receptors. Functionally, whereas NNC 01-0012 acts as a full or poor antagonist at D1C and D1A receptor-me...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71062593.x
更新日期：1998-12-01 00:00:00
abstract：:Dopamine and norepinephrine are involved in regulation of melatonin synthesis in the pineal gland. In bovine pineal gland, D1- and D2-dopaminergic and alpha 1-adrenergic receptors have been characterized pharmacologically in several laboratories, while beta 1-adrenergic receptors have been studied using physiological ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb06383.x
更新日期：1991-11-01 00:00:00
abstract：:CYP46A1 is a neuron-specific cytochrome P450 that plays a pivotal role in maintaining cholesterol homeostasis in the CNS. However, the molecular mechanisms underlying human CYP46A1 expression are still poorly understood, partly because of the lack of a cellular model that expresses high levels of CYP46A1. Our previous...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07577.x
更新日期：2012-01-01 00:00:00
abstract：:The protein kinase C γ (PKCγ) undergoes multistep activation and participates in various cellular processes in Purkinje cells. Perturbations in its phosphorylation state, conformation or localization can disrupt kinase signalling, such as in spinocerebellar ataxia type 14 (SCA14) that is caused by missense mutations i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12491
更新日期：2014-03-01 00:00:00
abstract：:Previous work has demonstrated that there is a selective increase in extracellular taurine in the brain during acute water intoxication. One aim of the present study was to investigate whether plasma taurine contributes to this increase. To this end, the concentrations of taurine, other amino acids, and ethanolamine (...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb08204.x
更新日期：1991-02-01 00:00:00
abstract：:The possibility that the mechanism of lead neurotoxicity may be at the level of transcription was investigated in PC12 cells. In electrophoretic mobility gel shift assays Pb2+ was found to increase activator protein-1 complex (AP-1) DNA binding activity in PC12 cells; the increase was time- and concentration-dependent...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0730187.x
更新日期：1999-07-01 00:00:00
abstract：:The processes of acetylation, phosphorylation, and methylation of nuclear proteins in cerebral hemispheres of 10- and 30-day-old rats were investigated. The experiments were carried out in vitro by measuring the incorporation of labeled precursors into histones and nonhistone chromosomal proteins (NHP) extracted from ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb08041.x
更新日期：1983-03-01 00:00:00
