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Acta Neuropathologica

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https://www.readbyqxmd.com/read/28108787/dimethyl-fumarate-accelerates-peripheral-nerve-regeneration-via-activation-of-the-anti-inflammatory-and-cytoprotective-nrf2-ho-1-signaling-pathway
#1
LETTER
Fabian Szepanowski, Daniel M Donaldson, Hans-Peter Hartung, Anne K Mausberg, Christoph Kleinschnitz, Bernd C Kieseier, Mark Stettner
No abstract text is available yet for this article.
January 20, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28097436/damaged-reward-areas-in-human-alcoholics-neuronal-proportion-decline-and-astrocyte-activation
#2
LETTER
Daniil Sarkisyan, Igor Bazov, Hiroyuki Watanabe, Olga Kononenko, Ann-Christine Syvänen, Gunter Schumann, Tatiana Yakovleva, Georgy Bakalkin
No abstract text is available yet for this article.
January 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28091722/hyperphosphorylated-tau-causes-reduced-hippocampal-ca1-excitability-by-relocating-the-axon-initial-segment
#3
Robert John Hatch, Yan Wei, Di Xia, Jürgen Götz
Hyperphosphorylated tau has a critical role in tauopathies such as Alzheimer's disease and frontotemporal dementia, impairing neuronal function and eventually leading to neurodegeneration. A critical role for tau is supported by studies in transgenic mouse models that express the P301L tau mutation found in cases of familial frontotemporal dementia, with the accumulation of hyperphosphorylated tau in the hippocampus causing reductions in hippocampal long-term potentiation and impairments in spatial learning and memory...
January 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28084518/prion-disease-experimental-models-and-reality
#4
REVIEW
Sebastian Brandner, Zane Jaunmuktane
The understanding of the pathogenesis and mechanisms of diseases requires a multidisciplinary approach, involving clinical observation, correlation to pathological processes, and modelling of disease mechanisms. It is an inherent challenge, and arguably impossible to generate model systems that can faithfully recapitulate all aspects of human disease. It is, therefore, important to be aware of the potentials and also the limitations of specific model systems. Model systems are usually designed to recapitulate only specific aspects of the disease, such as a pathological phenotype, a pathomechanism, or to test a hypothesis...
January 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28083634/tau-interactome-mapping%C3%A2-based-identification-of-otub1-as-tau-deubiquitinase-involved-in-accumulation-of-pathological-tau-forms-in-vitro-and-in-vivo
#5
Peng Wang, Gerard Joberty, Arjan Buist, Alexandre Vanoosthuyse, Ilie-Cosmin Stancu, Bruno Vasconcelos, Nathalie Pierrot, Maria Faelth-Savitski, Pascal Kienlen-Campard, Jean-Noël Octave, Marcus Bantscheff, Gerard Drewes, Diederik Moechars, Ilse Dewachter
Dysregulated proteostasis is a key feature of a variety of neurodegenerative disorders. In Alzheimer's disease (AD), progression of symptoms closely correlates with spatiotemporal progression of Tau aggregation, with "early" oligomeric Tau forms rather than mature neurofibrillary tangles (NFTs) considered to be pathogenetic culprits. The ubiquitin-proteasome system (UPS) controls degradation of soluble normal and abnormally folded cytosolic proteins. The UPS is affected in AD and is identified by genomewide association study (GWAS) as a risk pathway for AD...
January 12, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28078450/genome-wide-methylation-profiles-in-primary-intracranial-germ-cell-tumors-indicate-a-primordial-germ-cell-origin-for-germinomas
#6
Shintaro Fukushima, Satoshi Yamashita, Hisato Kobayashi, Hirokazu Takami, Kohei Fukuoka, Taishi Nakamura, Kai Yamasaki, Yuko Matsushita, Hiromi Nakamura, Yasushi Totoki, Mamoru Kato, Tomonari Suzuki, Kazuhiko Mishima, Takaaki Yanagisawa, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Masahiro Mizoguchi, Kaoru Tamura, Keiichi Sakai, Kazuhiko Sugiyama, Mitsutoshi Nakada, Kiyotaka Yokogami, Hideo Takeshima, Yonehiro Kanemura, Masahide Matsuda, Akira Matsumura, Kazuhiko Kurozumi, Keisuke Ueki, Masahiro Nonaka, Akio Asai, Nobutaka Kawahara, Yuichi Hirose, Tatusya Takayama, Yoichi Nakazato, Yoshitaka Narita, Tatsuhiro Shibata, Masao Matsutani, Toshikazu Ushijima, Ryo Nishikawa, Koichi Ichimura
Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling...
January 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28074274/glioma-experimental-models-and-reality
#7
REVIEW
Krissie Lenting, Roel Verhaak, Mark Ter Laan, Pieter Wesseling, William Leenders
In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in...
January 10, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28074273/experimental-models-of-neurological-disease-neuropathology-determines-what-is-virtual-reality-science-or-fiction
#8
EDITORIAL
Werner Paulus
No abstract text is available yet for this article.
January 10, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#9
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28064358/incipient-progressive-supranuclear-palsy-is-more-common-than-expected-and-may-comprise-clinicopathological-subtypes-a-forensic-autopsy-series
#10
Koji Yoshida, Yukiko Hata, Koshi Kinoshita, Shutaro Takashima, Kortaro Tanaka, Naoki Nishida
We investigated 998 serial Japanese forensic autopsy cases (0-101 years old, mean age 61.7 ± 21.9), with no case selection, using immunohistochemistry to detect cases with progressive supranuclear palsy (PSP). Twenty-nine cases (mean age 82.3 ± 7.2 years, 11 males, 18 females) fulfilled the National Institute of Neuronal Disorders and Stroke (NINDS)-PSP pathological criteria (2.9% of all cases, 4.6% of cases over 60). All had neuronal and glial inclusions in the basal ganglia and brainstem. However, 13 cases had low tau pathology and were categorized as atypical PSP...
January 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28064357/ischemic-stroke-experimental-models-and-reality
#11
REVIEW
Clemens J Sommer
The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel ("ischemic stroke") eventually leading to brain infarction. The final infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems and an adequate systemic blood pressure, etiology and localization of the infarct, but also on age, sex, comorbidities with the respective multimedication and genetic background...
January 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28058507/als-ftld-experimental-models-and-reality
#12
REVIEW
Rachel H Tan, Yazi D Ke, Lars M Ittner, Glenda M Halliday
Amyotrophic lateral sclerosis is characterised by a loss of upper and lower motor neurons and characteristic muscle weakness and wasting, the most common form being sporadic disease with neuronal inclusions containing the tar DNA-binding protein 43 (TDP-43). Frontotemporal lobar degeneration is characterised by atrophy of the frontal and/or temporal lobes, the most common clinical form being the behavioural variant, in which neuronal inclusions containing either TDP-43 or 3-repeat tau are most prevalent. Although the genetic mutations associated with these diseases have allowed various experimental models to be developed, the initial genetic forms identified remain the most common models employed to date...
January 5, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28058506/genome-wide-dna-methylation-profiling-identifies-primary-central-nervous-system-lymphoma-as-a-distinct-entity-different-from-systemic-diffuse-large-b-cell-lymphoma
#13
LETTER
Taishi Nakamura, Satoshi Yamashita, Kazutaka Fukumura, Jun Nakabayashi, Kazuhiro Tanaka, Kaoru Tamura, Kensuke Tateishi, Manabu Kinoshita, Shintaro Fukushima, Hirokazu Takami, Kohei Fukuoka, Kai Yamazaki, Yuko Matsushita, Makoto Ohno, Yasuji Miyakita, Soichiro Shibui, Atsuhiko Kubo, Takashi Shuto, Sylvia Kocialkowski, Shoji Yamanaka, Akitake Mukasa, Takashi Sasayama, Kazuhiko Mishima, Taketoshi Maehara, Nobutaka Kawahara, Motoo Nagane, Yoshitaka Narita, Hiroyuki Mano, Toshikazu Ushijima, Koichi Ichimura
No abstract text is available yet for this article.
January 5, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28032215/a-driver-role-for-gaba-metabolism-in-controlling-stem-and-proliferative-cell-state-through-ghb-production-in-glioma
#14
Elias A El-Habr, Luiz G Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation...
December 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28025715/alzheimer-s-disease-experimental-models-and-reality
#15
REVIEW
Eleanor Drummond, Thomas Wisniewski
Experimental models of Alzheimer's disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor...
December 26, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28012042/dihydropyridine-receptor-dhpr-cacna1s-congenital-myopathy
#16
Vanessa Schartner, Norma B Romero, Sandra Donkervoort, Susan Treves, Pinki Munot, Tyler Mark Pierson, Ivana Dabaj, Edoardo Malfatti, Irina T Zaharieva, Francesco Zorzato, Osorio Abath Neto, Guy Brochier, Xavière Lornage, Bruno Eymard, Ana Lía Taratuto, Johann Böhm, Hernan Gonorazky, Leigh Ramos-Platt, Lucy Feng, Rahul Phadke, Diana X Bharucha-Goebel, Charlotte Jane Sumner, Mai Thao Bui, Emmanuelle Lacene, Maud Beuvin, Clémence Labasse, Nicolas Dondaine, Raphael Schneider, Julie Thompson, Anne Boland, Jean-François Deleuze, Emma Matthews, Aleksandra Nadaj Pakleza, Caroline A Sewry, Valérie Biancalana, Susana Quijano-Roy, Francesco Muntoni, Michel Fardeau, Carsten G Bönnemann, Jocelyn Laporte
Muscle contraction upon nerve stimulation relies on excitation-contraction coupling (ECC) to promote the rapid and generalized release of calcium within myofibers. In skeletal muscle, ECC is performed by the direct coupling of a voltage-gated L-type Ca(2+) channel (dihydropyridine receptor; DHPR) located on the T-tubule with a Ca(2+) release channel (ryanodine receptor; RYR1) on the sarcoplasmic reticulum (SR) component of the triad. Here, we characterize a novel class of congenital myopathy at the morphological, molecular, and functional levels...
December 23, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28012041/brain-to-stomach-transfer-of-%C3%AE-synuclein-via-vagal-preganglionic-projections
#17
Ayse Ulusoy, Robert J Phillips, Michael Helwig, Michael Klinkenberg, Terry L Powley, Donato A Di Monte
Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical implications. Experiments were carried out to elucidate the relationship between α-synuclein accumulation in the brain and in peripheral organs, and to identify potential pathways involved in long-distance protein transfer. Results of this in vivo study revealed a route-specific transmission of α-synuclein from the rat brain to the stomach. Following targeted midbrain overexpression of human α-synuclein, the exogenous protein was capable of reaching the gastric wall where it was accumulated into preganglionic vagal terminals...
December 23, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28004278/histones-facilitate-%C3%AE-synuclein-aggregation-during-neuronal-apoptosis
#18
Peizhou Jiang, Ming Gan, Shu-Hui Yen, Pamela J McLean, Dennis W Dickson
Ample in vitro and in vivo experimental evidence supports the hypothesis that intercellular transmission of α-synuclein (αS) is a mechanism underlying the spread of αS pathology in Parkinson's disease and related disorders. What remains unexplained is where and how initial transmissible αS aggregates form. In a previous study, we demonstrated that αS aggregates rapidly form in neurons with impaired nuclear membrane integrity due to the interaction between nuclear proaggregant factor(s) and αS and that such aggregates may serve as a source for αS seeding...
December 21, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28004277/tauroursodeoxycholic-bile-acid-arrests-axonal-degeneration-by-inhibiting-the-unfolded-protein-response-in-x-linked-adrenoleukodystrophy
#19
Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme...
December 21, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28000032/gain-of-12p-encompassing-ccnd2-is-associated-with-gemistocytic-histology-in-idh-mutant-astrocytomas
#20
Felix Sahm, Andrey Korshunov, Daniel Schrimpf, Damian Stichel, David T W Jones, David Capper, Christian Koelsche, David Reuss, Annekathrin Kratz, Kristin Huang, Annika K Wefers, Matthias Schick, Melanie Bewerunge-Hudler, Michel Mittelbronn, Michael Platten, Daniel Hänggi, Astrid Jeibmann, Andreas Unterberg, Christel Herold-Mende, Stefan M Pfister, Sebastian Brandner, Wolfgang Wick, Andreas von Deimling
No abstract text is available yet for this article.
December 20, 2016: Acta Neuropathologica
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