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Journal of Neurochemistry

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https://www.readbyqxmd.com/read/28429406/haplodeficiency-of-cathepsin-d-does-not-affect-cerebral-amyloidosis-and-autophagy-in-app-ps1-transgenic-mice
#1
Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. The current study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in APPsw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease of Cat D level in APP/PS1/Ctsd+/- compared to APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429370/the-role-of-charged-residues-in-independent-glycine-receptor-folding-domains-for-intermolecular-interactions-and-ion-channel-function
#2
Georg Langlhofer, Carmen Villmann
Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4, and C-terminal sequences is essential for pentameric receptor arrangements. In vitro coexpressions of GlyRα1 truncated N-domains and C- domains were able to restore ion channel function. An ionic interaction between both domains was hypothesised as the underlying mechanism...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429368/-aralar-agc1-deficiency-a-neurodevelopmental-disorder-with-severe-impairment-of-neuronal-mitochondrial-respiration-does-not-produce-a-primary-increase-in-brain-lactate
#3
Inés Juaristi, María L García-Martin, Tiago B Rodrigues, Jorgina Satrústegui, Irene Llorente-Folch, Beatriz Pardo
ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at PND 17...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#4
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28421605/cholinergic-glutamatergic-co-transmission-in-striatal-cholinergic-interneurons-new-mechanisms-regulating-striatal-computation
#5
REVIEW
Ornela Kljakic, Helena Janickova, Vania F Prado, Marco A M Prado
It is well established that neurons secrete neuropeptides and ATP with classical neurotransmitters; however, certain neuronal populations are also capable of releasing two classical neurotransmitters by a process named co-transmission. Although there has been progress in our understanding of the molecular mechanism underlying co-transmission, the individual regulation of neurotransmitter secretion and the functional significance of this neuronal 'bilingualism' is still unknown. Striatal cholinergic interneurons (CINs) have been shown to secrete glutamate (Glu) in addition to acetylcholine (ACh) and are recognized for their role in the regulation of striatal circuits and behavior...
April 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28419454/the-de-novo-autism-spectrum-disorder-reln-r2290c-mutation-reduces-reelin-secretion-and-increases-protein-disulfide-isomerase-expression
#6
Dawn B Lammert, Frank A Middleton, Jen Pan, Eric C Olson, Brian W Howell
Despite the recent identification of over 40 missense heterozygous RELN mutations in ASD, none of these has been functionally characterized. Reelin is an integral signaling ligand for proper brain development and postnatal synapse function - properties likely disrupted in ASD patients. We find that the R2290C mutation, which arose de novo in an affected ASD proband, and other analogous mutations in RXR domains reduce protein secretion. Closer analysis of RELN R2290C heterozygous neurospheres reveals upregulation of Protein Disulfide Isomerase A1, best known as an ER-chaperone protein, which has been linked to neuronal pathology...
April 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28407315/drugs-with-antidepressant-properties-affect-tryptophan-metabolites-differently-in-rodent-models-with-depression-like-behavior
#7
Amanda Eskelund, Yan Li, David P Budac, Heidi K Müller, Gulinello Maria, Connie Sanchez, Gregers Wegener
The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line (FSL) rats, a genetic rat model of depression, and its controls: Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28407243/simulations-of-membrane-bound-diglycosylated-human-prion-protein-reveal-potential-protective-mechanisms-against-misfolding
#8
Chin Jung Cheng, Heidi Koldsø, Marc W Van der Kamp, Birgit Schiøtt, Valerie Daggett
Prion diseases are associated with the misfolding of the prion protein (PrP) from its normal cellular form (PrP(C) ) to its infectious scrapie form (PrP(S)(c) ). Posttranslational modifications of PrP in vivo can play an important role in modulating the process of misfolding. To gain more insight into the effects of posttranslational modifications on PrP structure and dynamics and to test the hypothesis that such modifications can interact with the protein, we have performed molecular dynamics simulations of diglycosylated human PrP(C) bound to a lipid bilayer via a glycophosphatidylinositol anchor...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28407242/the-role-of-autophagy-in-pro-inflammatory-responses-of-microglia-activation-via-mitochondrial-reactive-oxygen-species-in-vitro
#9
Junli Ye, Zhongxin Jiang, Xuehong Chen, Mengyang Liu, Jing Li, Na Liu
Microglia over-activation contributes to neurodegenerative processes by neurotoxin factors and pro-inflammatory molecules of pro-inflammatory processes. Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be involved in microglial activation, but the underlying mechanism is unclear. Here we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3-methyladenine treatment, siRNA-Beclin 1 or siRNA-ATG5 transfection) or induction (rapamycin treatment) in murine microglial BV-2 cells or cultured primary mouse microglial cells...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28398653/the-noble-gas-xenon-provides-protection-and-trophic-stimulation-to-midbrain-dopamine-neurons
#10
Jérémie Lavaur, Déborah Le Nogue, Marc Lemaire, Jan Pype, Géraldine Farjot, Etienne C Hirsch, Patrick P Michel
Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In the present study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease (PD). Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28397282/brain-aging-and-neurodegeneration-from-a-mitochondrial-point-of-view
#11
REVIEW
Amandine Grimm, Anne Eckert
Aging was defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the "free-radical theory of aging", because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species (ROS)...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28397252/is-sporadic-alzheimer-s-disease-a-developmental-disorder
#12
Thomas Arendt, Jens Stieler, Uwe Ueberham
Alzheimer's disease (AD) is a neurodegenerative disorder of higher age that specifically occurs in human. Its clinical phase, characterized by a decline in physiological, psychological and social functioning, is preceded by a long clinically silent phase of at least several decades that might perhaps even start very early in life. Overall, key functional abilities decline in AD patients in reverse order of the development of these abilities during childhood and adolescence. Early symptoms of AD, thus, typically affect mental functions that have been acquired only during very recent hominid evolution and as such are specific to human...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28397247/isogenic-blood-brain-barrier-models-based-on-patient-derived-stem-cells-display-inter-individual-differences-in-cell-maturation-and-functionality
#13
Ronak Patel, Shyanne Page, Abraham Jacob Al-Ahmad
The blood-brain barrier (BBB) constitutes an important component of the neurovascular unit formed by specialized brain microvascular endothelial cells (BMECs) surrounded by astrocytes, pericytes and neurons. Recently, isogenic in vitro models of the BBB based on human pluripotent stem cells have been documented, yet the impact of inter-individual variability on the yield and phenotype of such models remains to be documented. In this study, we investigated the impact of inter-individual variability on the yield and phenotype of isogenic models of the BBB, using patient-derived induced pluripotent stem cells (iPSCs)...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28397245/interactions-between-integrase-inhibitors-and-human-arginase-1
#14
Lucia Lisi, Michela Pizzoferrato, Fabiola Teresa Miscioscia, Alessandra Topai, Pierluigi Navarra
The neuro-pathogenic mechanism(s) underlying HIV-associated neurocognitive disorders are mostly unknown. HIV-infected macrophages and microglial cells play a crucial role and the metabolic fate of L-arginine may be highly relevant for microglia activation. In this context Arginase (ARG), which uses L-arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In the present study, we investigated whether Integrase Strand Transfer Inhibitors (INSTIs) share with the other antiretroviral drugs the ability to inhibit ARG activity...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28382744/exercise-and-bdnf-reduce-a%C3%AE-production-by-enhancing-%C3%AE-secretase-processing-of-app
#15
Saket M Nigam, Shaohua Xu, Joanna S Kritikou, Krisztina Marosi, Lennart Brodin, Mark P Mattson
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by aggregation of toxic forms of amyloid β peptide (Aβ). Treatment strategies have largely been focused on inhibiting the enzymes (β- and γ-secretases) that liberate Aβ from the amyloid precursor protein (APP). While evidence suggests that individuals who exercise regularly are at reduced risk for AD and studies of animal models demonstrate that running can ameliorate brain Aβ pathology and associated cognitive deficits, the underlying mechanisms are unknown...
April 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28382685/dimethyl-fumarate-ameliorates-myoclonus-stemming-from-protein-misfolding-in-oligodendrocytes
#16
Cherie M Southwood, Danielle M Garshott, Chelsea R Richardson, Navid Seraji-Bozorgzad, Andrew M Fribley, Alexander Gow
Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of preclinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology...
April 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28382676/natural-genomic-amplification-of-cholinesterase-genes-in-animals
#17
REVIEW
Arnaud Chatonnet, Nicolas Lenfant, Pascale Marchot, Murray E Selkirk
Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases...
April 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28376279/molecular-mechanisms-underlying-protective-effects-of-quercetin-against-mitochondrial-dysfunction-and-progressive-dopaminergic-neurodegeneration-in-cell-culture-and-mitopark-transgenic-mouse-models-of-parkinson-s-disease
#18
Muhammet Ay, Jie Luo, Monica Langley, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Quercetin, one of the major flavonoids in plants, has been recently reported to have neuroprotective effects against neurodegenerative processes. However, since the molecular signaling mechanisms governing these effects are not well clarified, we evaluated quercetin's effect on the neuroprotective signaling events in dopaminergic neuronal models and further tested its efficacy in the MitoPark transgenic mouse model of Parkinson's disease (PD). Western blotting analysis revealed that quercetin significantly induced the activation of two major cell survival kinases, protein kinase D1 (PKD1) and Akt in MN9D dopaminergic neuronal cells...
April 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28369944/increasing-acetyl-coa-metabolism-attenuates-injury-and-alters-spinal-cord-lipid-content-in-mice-subjected-to-experimental-autoimmune-encephalomyelitis
#19
Amber C Chevalier, Thad A Rosenberger
Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE)...
March 31, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28369888/early-growth-response-1-mediated-downregulation-of-drebrin-correlates-with-loss-of-dendritic-spines
#20
Chulmin Cho, Ryen MacDonald, Jijun Shang, Moon Jeong Cho, Lorraine E Chalifour, Hemant K Paudel
Postsynaptic dendritic spines are structurally composed of actin cytoskeleton, which undergoes dynamic morphological changes to accommodate incoming synaptic activity. Drebrin is an actin binding protein highly expressed in dendritic spines that serves an important role in regulating spine morphology. Functionally, loss of drebrin directly correlates with deficits in learning and memory, as is the case observed in Alzheimer's disease. Despite these findings, the regulatory factor responsible for drebrin loss remains unclear...
March 31, 2017: Journal of Neurochemistry
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