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https://www.readbyqxmd.com/read/28819074/-molecular-pathogenesis-of-polyglutamine-diseases
#1
Yuji Takahashi
Polyglutamine diseases result from gain-of-function mutations. The expanded polyglutamine tracts lead to conformational changes in proteins, resulting in their aggregation. The intermediates including monomers or oligomers, are more toxic than the aggregates to neurons. At the molecular level, protein misfolding, transcriptional dysregulation, deranged calcium homeostasis, impaired cytoskeleton/axonal transport, mitochondrial dysfunction, and RNA toxicity contribute to disease progression. Understanding the underlying pathogenesis facilitates development of therapy for polyglutamine diseases...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28814817/conjugated-polymers-mediate-effective-activation-of-the-mammalian-ion-channel-transient-receptor-potential-vanilloid-1
#2
F Lodola, N Martino, G Tullii, G Lanzani, M R Antognazza
Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801915/manganese-and-1-methyl-4-phenylpyridinium-mpp-induced-neurotoxicity-indicate-differences-in-morphological-electrophysiological-and-genome-wide-alterations-implications-for-idiopathic-parkinson-s-disease
#3
Rajeswara Babu Mythri, Narayana Reddy Raghunath, Santosh Chandrakant Narwade, Mirazkar DasharathaRao Pandareesh, Kollarkandi Rajesh Sabitha, Mohamad Aiyaz, Bipin Chand, Manas Sule, Krittika Ghosh, Senthil Kumar, Bhagyalakshmi Shankarappa, Soundarya Soundararajan, Phalguni Anand Alladi, Meera Purushottam, Narayanappa Gayathri, Deepti Dileep Deobagkar, Thenkanidiyoor Rao Laxmi, Srinivas Bharath Muchukunte Mukunda
Idiopathic Parkinson's disease (iPD) and manganese-induced atypical Parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the PD toxin 1-methyl-4-phenylpyridinium ion (MPP(+) ) and manganese (Mn) followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and Mn mouse models...
August 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#4
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28783680/arc-arg3-1-governs-inflammatory-dendritic-cell-migration-from-the-skin-and-thereby-controls-t-cell-activation
#5
Friederike Ufer, Pablo Vargas, Jan Broder Engler, Joseph Tintelnot, Benjamin Schattling, Hana Winkler, Simone Bauer, Nina Kursawe, Anne Willing, Oliver Keminer, Ora Ohana, Gabriela Salinas-Riester, Ole Pless, Dietmar Kuhl, Manuel A Friese
Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly confined to migDCs...
September 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/28772119/the-biology-of-forgetting-a-perspective
#6
REVIEW
Ronald L Davis, Yi Zhong
Pioneering research studies, beginning with those using Drosophila, have identified several molecular and cellular mechanisms for active forgetting. The currently known mechanisms for active forgetting include neurogenesis-based forgetting, interference-based forgetting, and intrinsic forgetting, the latter term describing the brain's chronic signaling systems that function to slowly degrade molecular and cellular memory traces. The best-characterized pathway for intrinsic forgetting includes "forgetting cells" that release dopamine onto engram cells, mobilizing a signaling pathway that terminates in the activation of Rac1/Cofilin to effect changes in the actin cytoskeleton and neuron/synapse structure...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28767038/microtubule-dependent-ribosome-localization-in-c-elegans-neurons
#7
Kentaro Noma, Alexandr Goncharov, Mark H Ellisman, Yishi Jin
Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28765051/how-does-calcium-interact-with-the-cytoskeleton-to-regulate-growth-cone-motility-during-axon-pathfinding
#8
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/28754891/cyclin-dependent-kinase-5-novel-role-of-gene-variants-identified-in-adhd
#9
Subhamita Maitra, Mahasweta Chatterjee, Swagata Sinha, Kanchan Mukhopadhyay
Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744327/mir-196a-enhances-neuronal-morphology-through-suppressing-ranbp10-to-provide-neuroprotection-in-huntington-s-disease
#10
Lu-Shiun Her, Su-Han Mao, Chih-Yi Chang, Pei-Hsun Cheng, Yu-Fan Chang, Han-In Yang, Chuan-Mu Chen, Shang-Hsun Yang
MicroRNAs (miRNAs) play important roles in several neurobiological processes, including the development and progression of diseases. Previously, we identified that one specific miRNA, miR-196a, provides neuroprotective effects on Huntington's disease (HD), although the detailed mechanism is still unclear. Based on our bioinformatic analyses, we hypothesize miR-196a might offer neuroprotective functions through improving cytoskeletons of brain cells. Here, we show that miR-196a could enhance neuronal morphology, further ameliorating intracellular transport, synaptic plasticity, neuronal activity, and learning and memory abilities...
2017: Theranostics
https://www.readbyqxmd.com/read/28740252/decelerated-neurodegeneration-after-intravitreal-injection-of-%C3%AE-synuclein-antibodies-in-a-glaucoma-animal-model
#11
J Teister, F Anders, S Beck, S Funke, H von Pein, V Prokosch, N Pfeiffer, F Grus
Although elevated intraocular pressure (IOP) remains the major risk factor in glaucoma, neurodegenerative processes continue despite effective IOP lowering. Altered α-synuclein antibody (Abs) levels have been reported to play a crucial role. This study aimed at identifying whether α-synuclein Abs are capable to decelerate neuronal decay while providing insights into proteomic changes. Four groups of Sprague Dawley rats received episcleral vein occlusion: (1) CTRL, no intravitreal injection, n = 6, (2) CTRL IgG, intravitreal injection of unspecific IgG, n = 5, (3) Buffer, intravitreal injection of buffer, n = 6, (4), α-synuclein Ab, intravitreal injection of α-synuclein Ab, n = 5...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736134/stimulus-evoked-erk-dependent-phosphorylation-of-activity-regulated-cytoskeleton-associated-protein-arc-regulates-its-neuronal-subcellular-localization
#12
Oleksii Nikolaienko, Maria Steene Eriksen, Sudarshan Patil, Haruhiko Bito, Clive R Bramham
Activity-regulated cytoskeletal-associated protein (Arc) is implicated as a master regulator of long-term synaptic plasticity and memory formation in mammalian brain. Arc acts at synapses and within the nucleus, but the mechanisms controlling Arc localization and function are little known. As Arc transcription and translation are regulated by extracellularsignal-regulated kinase (ERK) signaling, we asked whether Arc protein itself is phosphorylated by ERK. GST-fused Arc of rat origin was able to pull down endogenous ERK2 from rat hippocampal lysates...
July 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28720664/dynein-efficiently-navigates-the-dendritic-cytoskeleton-to-drive-the-retrograde-trafficking-of-bdnf-trkb-signaling-endosomes
#13
Swathi Ayloo, Pedro Guedes-Dias, Amy E Ghiretti, Erika L F Holzbaur
The efficient transport of cargoes within axons and dendrites is critical for neuronal function. While we have a basic understanding of axonal transport, much less is known about transport in dendrites. We employed an optogenetic approach to recruit motor proteins to cargo in real time within axons or dendrites in hippocampal neurons. Kinesin-1, a robust axonal motor, moves cargo less efficiently in dendrites. In contrast, cytoplasmic dynein efficiently navigates both axons and dendrites; in both compartments, dynamic microtubule plus-ends enhance dynein-dependent transport...
July 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28719878/the-effects-of-fluoride-on-neuronal-function-occurs-via-cytoskeleton-damage-and-decreased-signal-transmission
#14
Lingli Chen, Hongmei Ning, Zhihong Yin, Xiaochao Song, Yongchao Feng, Hao Qin, Yi Li, Jundong Wang, Yaming Ge, Wenkui Wang
It has been reported that fluoride exposure may cause serious public health problems, particularly neurotoxicity. However, the underlying mechanisms remain unclear. This study used Neuro-2A cells to investigate the effects of fluoride on the cytoskeleton. The Neuro-2A cells were exposed to 0, 1, 2, 4 and 6 mM sodium fluoride (NaF) for 24 h. Cell viability and lactate dehydrogenase (LDH) release were examined. It was observed that exposure to NaF reduced cell viability, disrupted cellular membrane integrity, and high levels of LDH were released...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28703738/abnormally-increased-secretion-in-olfactory-neuronal-precursors-from-a-case-of-schizophrenia-is-modulated-by-melatonin-a-pilot-study
#15
Montserrat G Cercós, Tania Galván-Arrieta, Marcela Valdés-Tovar, Héctor Solís-Chagoyán, Jesús Argueta, Gloria Benítez-King, Citlali Trueta
The alterations that underlie the pathophysiology of schizophrenia (SCZ) include the dysregulation of structural and functional properties of neurons. Among these, the secretion of neurotransmitters and hormones, which plays a key role for neuronal communication and development, is altered. Neuronal precursors from the human olfactory epithelium have been recently characterized as a reliable model for studying the etiopathogenesis of neuropsychiatric diseases. Our previous work has shown that melatonin enhances the development of morphological and functional features of cloned olfactory neuronal precursors (ONPs) from a healthy subject...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28701913/common-hepatic-branch-of-vagus-nerve-dependent-expression-of-immediate-early-genes-in-the-mouse-brain-by-intraportal-l-arginine-comparison-with-cholecystokinin-8
#16
Daisuke Yamada, Peter Koppensteiner, Saori Odagiri, Megumi Eguchi, Shun Yamaguchi, Tetsuya Yamada, Hideki Katagiri, Keiji Wada, Masayuki Sekiguchi
Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV) is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28700939/neogenin-recruitment-of-the-wave-regulatory-complex-to-ependymal-and-radial-progenitor-adherens-junctions-prevents-hydrocephalus
#17
Conor J O'Leary, Cathrin C Nourse, Natalie K Lee, Amanda White, Michael Langford, Kai Sempert, Stacey J Cole, Helen M Cooper
Denudation of the ependyma due to loss of cell adhesion mediated by cadherin-based adherens junctions is a common feature of perinatal hydrocephalus. Junctional stability depends on the interaction between cadherins and the actin cytoskeleton. However, the molecular mechanism responsible for recruiting the actin nucleation machinery to the ependymal junction is unknown. Here, we reveal that loss of the netrin/RGM receptor, Neogenin, leads to severe hydrocephalus. We show that Neogenin plays a critical role in actin nucleation in the ependyma by anchoring the WAVE regulatory complex (WRC) and Arp2/3 to the cadherin complex...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28692740/switching-of-%C3%AE-catenin-from-epithelial-to-neuronal-type-during-lens-epithelial-cell-differentiation
#18
Rupalatha Maddala, Ponugoti Vasantha Rao
Purpose: Ocular lens fiber cell elongation, differentiation, and compaction are associated with extensive reorganization of cell adhesive interactions and cytoskeleton; however, our knowledge of proteins critical to these events is still evolving. This study characterizes the distribution pattern of neuronal-specific α-catenin (αN-catenin) and its interaction with the N-cadherin-associated adherens junctions (AJs) and their stability in the mouse lens fibers. Methods: Expression and distribution of αN-catenin in developing mouse and adult human lenses was determined by RT-PCR, immunoblot, and immunofluorescence analyses...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28690500/dysregulation-of-microtubule-stability-impairs-morphofunctional-connectivity-in-primary-neuronal-networks
#19
Peter Verstraelen, Jan R Detrez, Marlies Verschuuren, Jacobine Kuijlaars, Rony Nuydens, Jean-Pierre Timmermans, Winnok H De Vos
Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number and strength of synaptic connections is tightly regulated. Synapse function relies on the microtubule (MT) cytoskeleton, the dynamics of which are in turn controlled by a plethora of MT-associated proteins, including the MT-stabilizing protein Tau. Although mutations in the Tau-encoding MAPT gene underlie a set of neurodegenerative disorders, termed tauopathies, the exact contribution of MT dynamics and the perturbation thereof to neuronal network connectivity has not yet been scrutinized...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28681095/nail-patella-syndrome
#20
REVIEW
Ralph Witzgall
The pathognomonic symptoms of patients with nail-patella syndrome are their small or absent patellae and dysplastic or absent finger- and toenails. Many of the patients suffer from renal symptoms which also affect their prognosis. In 1998, mutations in the gene encoding the transcription factor LMX1B were identified as underlying this autosomal-dominant disease. The LMX1B gene is expressed in a variety of tissues, and the symptoms are reflected nicely by its expression pattern. LMX1B is essential for dorso-ventral pattern formation in the limbs, for differentiation of the anterior portions of the eyes, for development of certain neuron populations in the central nervous system, and for the differentiation and maintenance of podocytes...
August 2017: Pflügers Archiv: European Journal of Physiology
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