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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/28811225/alpha-synuclein-ferrireductase-activity-is-detectible-in-vivo-is-altered-in-parkinson-s-disease-and-increases-the-neurotoxicity-of-dopal
#1
Jennifer S McDowall, Ioanna Ntai, Kevin C Honeychurch, John P Hart, Philippe Colin, Bernard L Schneider, David R Brown
The normal cellular role of α-synuclein is of potential importance in understanding diseases in which an aggregated form of the protein has been implicated. A potential loss or change in the normal function of α-synuclein could play a role in the aetiology of diseases such as Parkinson's disease. Recently, it has been suggested that α-synuclein could cause the enzymatic reduction of iron and a cellular increase in Fe(II) levels. Experiments were carried out to determine if such activity could be determined in vivo...
August 12, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28784263/ena-vasp-proteins-regulate-exocytosis-by-mediating-myosin-vi-dependent-recruitment-of-secretory-granules-to-the-cortical-actin-network
#2
Vanesa M Tomatis, Peter Josh, Andreas Papadopulos, Rachel S Gormal, Vanessa Lanoue, Sally Martin, Frédéric A Meunier
In neurosecretory cells, myosin VI associated with secretory granules (SGs) mediates their activity-dependent recruitment to the cortical actin network and is necessary to sustain exocytosis. The mechanism by which myosin VI interacts with SGs is unknown. Using a myosin VI pull-down assay and mass spectrometry we identified Mena, a member of the ENA/VASP family, as a myosin VI binding partner in PC12 cells, and confirmed that Mena colocalized with myosin VI on SGs. Using a knock-sideways approach to inactivate the ENA/VASP family members by mitochondrial relocation, we revealed a concomitant redistribution of myosin VI...
August 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28768144/the-c-terminal-domain-of-zdhhc2-contains-distinct-sorting-signals-that-regulate-intracellular-localisation-in-neurons-and-neuroendocrine-cells
#3
Christine Salaun, Louise Ritchie, Jennifer Greaves, Trevor J Bushell, Luke H Chamberlain
The S-acyltransferase zDHHC2 mediates dynamic S-acylation of PSD95 and AKAP79/150, which impacts synaptic targeting of AMPA receptors. zDHHC2 is responsive to synaptic activity and catalyses the increased S-acylation of PSD95 that occurs following action potential blockade or application of ionotropic glutamate receptor antagonists. These treatments have been proposed to increase plasma membrane delivery of zDHHC2 via an endosomal cycling pathway, enhancing substrate accessibility. To generate an improved understanding of zDHHC2 trafficking and how this might be regulated by neuronal activity, we searched for intramolecular signals that regulate enzyme localisation...
July 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28765051/how-does-calcium-interact-with-the-cytoskeleton-to-regulate-growth-cone-motility-during-axon-pathfinding
#4
REVIEW
Robert J Gasperini, Macarena Pavez, Adrian C Thompson, Camilla B Mitchell, Holly Hardy, Kaylene M Young, John K Chilton, Lisa Foa
The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved...
July 29, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28743452/transcriptional-profiles-for-distinct-aggregation-states-of-mutant-huntingtin-exon-1-protein-unmask-new-huntington-s-disease-pathways
#5
Nagaraj S Moily, Angelique R Ormsby, Aleksandar Stojilovic, Yasmin M Ramdzan, Jeannine Diesch, Ross D Hannan, Michelle S Zajac, Anthony J Hannan, Alicia Oshlack, Danny M Hatters
Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The central feature of Huntington's disease pathology is the aggregation of mutant Huntingtin (Htt) protein into micrometer-sized inclusion bodies. Soluble mutant Htt states are most proteotoxic and trigger an enhanced risk of death whereas inclusions confer different changes to cellular health, and may even provide adaptive responses to stress. Yet the molecular mechanisms underpinning these changes remain unclear...
July 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28733129/endocannabinoids-exert-cb1-receptor-mediated-neuroprotective-effects-in-models-of-neuronal-damage-induced-by-hiv-1-tat-protein
#6
Changqing Xu, Douglas J Hermes, Blessing Nwanguma, Ian R Jacobs, Kenneth Mackie, Somnath Mukhopadhyay, Aron H Lichtman, Bogna Ignatowska-Jankowska, Sylvia Fitting
In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND...
July 19, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28720530/downregulation-of-protein-phosphatase-2a-by-apolipoprotein-e-implications-for-alzheimer-s-disease
#7
Veena Theendakara, Dale E Bredesen, Rammohan V Rao
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity...
July 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28690173/immediate-and-delayed-hyperbaric-oxygen-therapy-as-a-neuroprotective-treatment-for-traumatic-brain-injury-in-mice
#8
Renana Baratz-Goldstein, Shlomi Toussia-Cohen, Aviya Elpaz, Vardit Rubovitch, Chaim G Pick
BACKGROUND: Traumatic brain injury is the most common cause of death or chronic disability among people under-35-years-old. There is no effective pharmacological treatment currently existing for TBI. Hyperbaric oxygen therapy (HBOT) is defined as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized higher than 1atm. HBOT offers physiological and mechanical effects by inducing a state of increased pressure and hyperoxia. HBOT has been proposed as an effective treatment for moderate traumatic brain injury (mTBI), yet the exact therapeutic window and mechanism that underlies this effect is not completely understood...
July 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28687523/tdp-43-in-the-spectrum-of-mnd-ftld-pathologies
#9
REVIEW
Lanier Heyburn, Charbel E-H Moussa
The relationship between RNA-binding proteins, particularly TAR DNA binding protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP-43 is involved in so many cellular processes that perturbation of protein homeostasis can lead to countless downstream effects. Understanding what leads to this disease-related protein imbalance and the resulting cellular and molecular effects will help to develop targets for disease intervention, whether it be prevention of protein accumulation, or addressing a secondary effect of protein accumulation...
July 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28684360/regulator-of-g-protein-signaling-5-rgs5-inhibits-sonic-hedgehog-function-in-mouse-cortical-neurons
#10
Chuanliang Liu, Qiongqiong Hu, Jia Jing, Yun Zhang, Jing Jin, Liulei Zhang, Lili Mu, Yumei Liu, Bo Sun, Tongshuai Zhang, Qingfei Kong, Guangyou Wang, Dandan Wang, Yao Zhang, Xijun Liu, Wei Zhao, Jinghua Wang, Tao Feng, Hulun Li
Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth...
July 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28676376/cutaneous-inflammation-regulates-thik1-expression-in-small-c-like-nociceptor-dorsal-root-ganglion-neurons
#11
William Haskins, Sergio Benitez, Juan M Mercado, Cristian G Acosta
Tandem pore-domain Halothane Inhibited K(+) channel (THIK1) is a two-pore-domain potassium channel (K2P) present in dorsal root ganglia (DRG). We previously demonstrated that THIK1 mRNA levels in the DRG dropped ipsilaterally 1day after CFA-induced cutaneous inflammation (CFA1). In this study we aimed to identify the currently unknown DRG subpopulations expressing THIK1, and to investigate the relationship between the channel and both inflammatory and spontaneous pain in normal rats. Using a combination of immunohistochemistry, western blotting and behavioural tests, we found that all small neurons and large groups of medium and large DRG neurons express THIK1...
July 1, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28673772/methyl-4-phenylpyridinium-mpp-differentially-affects-monoamine-release-and-re-uptake-in-murine-embryonic-stem-cell-derived-dopaminergic-and-serotonergic-neurons
#12
Yasmina Martí, Friederike Matthaeus, Thorsten Lau, Patrick Schloss
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to selectively damage dopaminergic (DA) cells in the substantia nigra and to produce symptoms which are alike to those observed in Parkinson's disease (PD). Based on the similarity between MPTP-induced neurotoxicity and PD-related neuropathology, application of MPTP or its metabolite methyl-4-phenylpyridinium (MPP+) was successfully established in experimental rodent models to study PD-related neurodegenerative events. MPP+ is taken up by the dopamine transporter (DAT) into DA neurons where it exerts its neurotoxic action on mitochondria by affecting complex I of the respiratory chain...
June 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28669622/smad4-is-essential-for-directional-progression-from-committed-neural-progenitor-cells-through-neuronal-differentiation-in-the-postnatal-mouse-brain
#13
Motoko Kawaguchi-Niida, Noriyuki Shibata, Yasuhide Furuta
Signaling by the TGFβ super-family, consisting of TGFβ/activin- and bone morphogenetic protein (BMP) branch pathways, is involved in the central nervous system patterning, growth, and differentiation during embryogenesis. Neural progenitor cells are implicated in various pathological conditions, such as brain injury, infarction, Parkinson's disease and Alzheimer's disease. However, the roles of TGFβ/BMP signaling in the postnatal neural progenitor cells in the brain are still poorly understood. We examined the functional contribution of Smad4, a key integrator of TGFβ/BMP signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ)...
June 29, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28666963/a-novel-kcna1-mutation-in-a-patient-with-paroxysmal-ataxia-myokymia-painful-contractures-and-metabolic-dysfunctions
#14
Paola Imbrici, Concetta Altamura, Francesca Gualandi, Giuseppe Felice Mangiatordi, Marcella Neri, Giovanni De Maria, Alessandra Ferlini, Alessandro Padovani, Maria Cristina D'Adamo, Orazio Nicolotti, Mauro Pessia, Diana Conte, Massimiliano Filosto, Jean-Francois Desaphy
Episodic ataxia type 1 (EA1) is a human dominant neurological syndrome characterized by continuous myokymia, episodic attacks of ataxic gait and spastic contractions of skeletal muscles that can be triggered by emotional stress and fatigue. This rare disease is caused by missense mutations in the KCNA1 gene coding for the neuronal voltage gated potassium channel Kv1.1, which contributes to nerve cell excitability in the cerebellum, hippocampus, cortex and peripheral nervous system. We identified a novel KCNA1 mutation, E283K, in an Italian proband presenting with paroxysmal ataxia and myokymia aggravated by painful contractures and metabolic dysfunctions...
June 28, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28666962/decreased-calcium-flux-in-niemann-pick-type-c1-patient-specific-ipsc-derived-neurons-due-to-higher-amount-of-calcium-impermeable-ampa-receptors
#15
Michael Rabenstein, Franziska Peter, Sarah Joost, Michaela Trilck, Arndt Rolfs, Moritz J Frech
Niemann-Pick disease type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene, resulting mainly in the accumulation of cholesterol and the ganglioside GM2. Recently, we described accumulations of these lipids in neuronal differentiated cells derived from NPC1 patient-specific induced pluripotent stem cells (iPSCs). As these lipids are essential for proper cell membrane composition, we were interested in the expression and function of voltage-gated ion channels and excitatory AMPA receptors (AMPARs) in neurons derived from three patient-specific iPSC lines...
June 27, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28642089/involvement-of-mapk-akt-gsk-3%C3%AE-and-ampk-mtor-signaling-pathways-in-protection-of-remote-glial-cells-from-axotomy-induced-necrosis-and-apoptosis-in-the-isolated-crayfish-stretch-receptor
#16
E V Berezhnaya, M Y Bibov, M A Komandirov, M A Neginskaya, M V Rudkovskii, A B Uzdensky
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells...
June 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28600222/taste-bud-derived-bdnf-maintains-innervation-of-a-subset-of-trkb-expressing-gustatory-nerve-fibers
#17
Tao Tang, Jennifer Rios-Pilier, Robin Krimm
Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF...
June 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28554564/the-third-wave-intermediate-filaments-in-the-maturing-nervous-system
#18
REVIEW
Matthew T K Kirkcaldie, Samuel T Dwyer
Intermediate filaments are critical for the extreme structural specialisations of neurons, providing integrity in dynamic environments and efficient communication along axons a metre or more in length. As neurons mature, an initial expression of nestin and vimentin gives way to α-internexin and the neurofilament triplet proteins, substituted by peripherin in axons outside the CNS, physically consolidating axons as they elongate and find their targets. Once connection is established, these proteins are transported, assembled, stabilised and modified, structurally transforming axons and dendrites as they acquire their full function...
May 26, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28552342/interplay-between-mitochondrial-metabolism-and-oxidative-stress-in-ischemic-stroke-an-epigenetic-connection
#19
REVIEW
Parimala Narne, Vimal Pandey, Prakash Babu Phanithi
The advent of epigenetics brought in a tectonic shift in the understanding of molecular basis of complex diseases like ischemic stroke (IS). Substantial scientific inquiry into the epigenetic basis of neurodegenerative diseases has bolstered the idea that altered carbon flux into central carbon metabolism and disturbed redox states govern the attendant transcriptional profiles through stochastic epigenetic changes. In view of an increasing understanding of the link between mitochondrial energy metabolism, oxidative stress and epigenetics in IS, the hitherto underappreciated 'neuroenergetics' is gaining sustained attention...
May 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28545680/a-role-for-tropomyosins-in-activity-dependent-bulk-endocytosis
#20
REVIEW
R S Gormal, N Valmas, T Fath, F A Meunier
Bulk endocytosis allows stimulated neurons to take up a large portion of the presynaptic plasma membrane in order to regenerate synaptic vesicle pools. Actin, one of the most abundant proteins in eukaryotic cells, plays an important role in this process, but a detailed mechanistic understanding of the involvement of the cortical actin network is still lacking, in part due to the relatively small size of nerve terminals and the limitation of optical microscopy. We recently discovered that neurosecretory cells display a similar, albeit much larger, form of bulk endocytosis in response to secretagogue stimulation...
May 22, 2017: Molecular and Cellular Neurosciences
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