keyword
MENU ▼
Read by QxMD icon Read
search

Tdp

keyword
https://www.readbyqxmd.com/read/28421535/microrna-metabolism-and-dysregulation-in-amyotrophic-lateral-sclerosis
#1
REVIEW
Paola Rinchetti, Mafalda Rizzuti, Irene Faravelli, Stefania Corti
MicroRNAs (miRNAs) are a subset of endogenous, small, non-coding RNA molecules involved in the post-transcriptional regulation of eukaryotic gene expression. Dysregulation in miRNA-related pathways in the central nervous system (CNS) is associated with severe neuronal injury and cell death, which can lead to the development of neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). ALS is a fatal adult onset disease characterized by the selective loss of upper and lower motor neurons. While the pathogenesis of ALS is still largely unknown, familial ALS forms linked to TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) gene mutations, as well as sporadic forms, display changes in several steps of RNA metabolism, including miRNA processing...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28417327/influence-of-land-use-and-land-cover-on-the-spatial-variability-of-dissolved-organic-matter-in-multiple-aquatic-environments
#2
Shatrughan Singh, Padmanava Dash, Saurav Silwal, Gary Feng, Ardeshir Adeli, Robert J Moorhead
Water quality of lakes, estuaries, and coastal areas serves as an indicator of the overall health of aquatic ecosystems as well as the health of the terrestrial ecosystem that drains to the water body. Land use and land cover plays not only a significant role in controlling the quantity of the exported dissolved organic matter (DOM) but also influences the quality of DOM via various biogeochemical and biodegradation processes. We examined the characteristics and spatial distribution of DOM in five major lakes, in an estuary, and in the coastal waters of the Mississippi, USA, and investigated the influence of the land use and land cover of their watersheds on the DOM composition...
April 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28416393/tdp-43-expression-influences-amyloid%C3%AE-plaque-deposition-and-tau-aggregation
#3
Stephani A Davis, Kok Ann Gan, James A Dowell, Nigel J Cairns, Michael A Gitcho
Although the main focus in Alzheimer's disease (AD) has been an investigation of mechanisms causing Aβ plaque deposition and tau tangle formation, recent studies have shown that phosphorylated TDP-43 pathology is present in up to 50% of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been associated with more severe AD pathology. Therefore, we hypothesized that TDP-43 may regulate amyloid-beta precursor protein (APP) trafficking and tau phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we developed a transgenic mouse that overexpresses hippocampal and cortical neuronal TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and presenilin 1 (PSEN1ΔE9)...
April 14, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28409281/spinal-poly-ga-inclusions-in-a-c9orf72-mouse-model-trigger-motor-deficits-and-inflammation-without-neuron-loss
#4
Martin H Schludi, Lore Becker, Lillian Garrett, Tania F Gendron, Qihui Zhou, Franziska Schreiber, Bastian Popper, Leda Dimou, Tim M Strom, Juliane Winkelmann, Anne von Thaden, Kristin Rentzsch, Stephanie May, Meike Michaelsen, Benjamin M Schwenk, Jing Tan, Benedikt Schoser, Marianne Dieterich, Leonard Petrucelli, Sabine M Hölter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Thomas Klopstock, Thomas Arzberger, Dieter Edbauer
Translation of the expanded (ggggcc)n repeat in C9orf72 patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA inclusions. To elucidate their role in pathogenesis, we generated transgenic mice expressing codon-modified (GA)149 conjugated with cyan fluorescent protein (CFP). Transgenic mice progressively developed poly-GA inclusions predominantly in motoneurons and interneurons of the spinal cord and brain stem and in deep cerebellar nuclei. Poly-GA co-aggregated with p62, Rad23b and the newly identified Mlf2, in both mouse and patient samples...
April 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28405995/recurrent-ventricular-tachycardia-due-to-long-qt-syndrome
#5
Rambabu Singh, Kshitiz Nath, Archana
Long QT syndrome (LQTS) is a rare inherited heart condition in which delayed repolarization of the heart following a heartbeat, increases the risk of episodes of Torsades de pointes (TdP, a form of irregular heartbeat that originates from the ventricles). These episodes may lead to palpitations, fainting, and sudden death due to ventricular fibrillation. Episodes may be provoked by various stimuli, depending on the subtype of the condition. We are reporting a case of 37 years old male whom we diagnosed to have long QT syndrome on the basis of clinical and ECG findings...
December 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28405022/therapeutic-reduction-of-ataxin-2-extends-lifespan-and-reduces-pathology-in-tdp-43-mice
#6
Lindsay A Becker, Brenda Huang, Gregor Bieri, Rosanna Ma, David A Knowles, Paymaan Jafar-Nejad, James Messing, Hong Joo Kim, Armand Soriano, Georg Auburger, Stefan M Pulst, J Paul Taylor, Frank Rigo, Aaron D Gitler
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that is characterized by motor neuron loss and that leads to paralysis and death 2-5 years after disease onset. Nearly all patients with ALS have aggregates of the RNA-binding protein TDP-43 in their brains and spinal cords, and rare mutations in the gene encoding TDP-43 can cause ALS. There are no effective TDP-43-directed therapies for ALS or related TDP-43 proteinopathies, such as frontotemporal dementia. Antisense oligonucleotides (ASOs) and RNA-interference approaches are emerging as attractive therapeutic strategies in neurological diseases...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#7
Riccardo Cristofani, Valeria Crippa, Paola Rusmini, Maria Elena Cicardi, Marco Meroni, Nausicaa V Licata, Gessica Sala, Elisa Giorgetti, Christopher Grunseich, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Carlo Ferrarese, Serena Carra, Angelo Poletti
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial...
April 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28401333/interactions-of-pathological-proteins-in-neurodegenerative-diseases
#8
REVIEW
Tara L Spires-Jones, Johannes Attems, Dietmar Rudolf Thal
Neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTD), Lewy body disease (LBD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have in common that protein aggregates represent pathological hallmark lesions. Amyloid β-protein, τ-protein, α-synuclein, and TDP-43 are the most frequently aggregated proteins in these disorders. Although they are assumed to form disease-characteristic aggregates, such as amyloid plaques and neurofibrillary tangles in AD or Lewy bodies in LBD/PD, they are not restricted to these clinical presentations...
April 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28396410/spinal-motor-neuron-protein-supersaturation-patterns-are-associated-with-inclusion-body-formation-in-als
#9
Prajwal Ciryam, Isabella A Lambert-Smith, Daniel M Bean, Rosie Freer, Fernando Cid, Gian Gaetano Tartaglia, Darren N Saunders, Mark R Wilson, Stephen G Oliver, Richard I Morimoto, Christopher M Dobson, Michele Vendruscolo, Giorgio Favrin, Justin J Yerbury
Amyotrophic lateral sclerosis (ALS) is a heterogeneous degenerative motor neuron disease linked to numerous genetic mutations in apparently unrelated proteins. These proteins, including SOD1, TDP-43, and FUS, are highly aggregation-prone and form a variety of intracellular inclusion bodies that are characteristic of different neuropathological subtypes of the disease. Contained within these inclusions are a variety of proteins that do not share obvious characteristics other than coaggregation. However, recent evidence from other neurodegenerative disorders suggests that disease-affected biochemical pathways can be characterized by the presence of proteins that are supersaturated, with cellular concentrations significantly greater than their solubilities...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395086/regional-overlap-of-pathologies-in-lewy-body-disorders
#10
Martí Colom-Cadena, Oriol Grau-Rivera, Lluís Planellas, Catalina Cerquera, Estrella Morenas, Sergio Helgueta, Laia Muñoz, Jaime Kulisevsky, Maria Jose Martí, Eduard Tolosa, Jordi Clarimon, Alberto Lleó, Ellen Gelpi
Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems. The brains of patients with LBD often display other comorbid pathologies, i.e. insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD). The incidence and physiological relevance of these concurrent pathological findings remain controversial. We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies)...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28389532/rna-binding-proteins-with-prion-like-domains-in-health-and-disease
#11
REVIEW
Alice Ford Harrison, James Shorter
Approximately 70 human RNA-binding proteins (RBPs) contain a prion-like domain (PrLD). PrLDs are low-complexity domains that possess a similar amino acid composition to prion domains in yeast, which enable several proteins, including Sup35 and Rnq1, to form infectious conformers, termed prions. In humans, PrLDs contribute to RBP function and enable RBPs to undergo liquid-liquid phase transitions that underlie the biogenesis of various membraneless organelles. However, this activity appears to render RBPs prone to misfolding and aggregation connected to neurodegenerative disease...
April 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28384473/sca31-flies-perform-in-a-balancing-act-between-ran-translation-and-rna-binding-proteins
#12
George R Jackson
In this issue of Neuron, Ishiguro et al. (2017) explore the toxicity of RAN translation in spinocerebellar ataxia 31. Using a Drosophila model, the authors demonstrate that TDP-43 and other RNA-binding proteins act as chaperones to regulate the formation of toxic RNA aggregates.
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28383310/short-term-variability-of-repolarization-is-superior-to-other-repolarization-parameters-in-the-evaluation-of-diverse-antiarrhythmic-interventions-in-the-chronic-av-block-dog
#13
A Bossu, R Varkevisser, Hdm Beekman, Mjc Houtman, Mag van der Heyden, M A Vos
Short-term variability (STV), to quantify beat-to-beat variability of repolarization (BVR), is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed, but also in vulnerable patients with heart failure or drug-induced long QT syndrome. In the CAVB dog model, STV can specifically distinguish between safe and unsafe drugs in proarrhythmic screening. Conversely, this dog model also offers the possibility to evaluate antiarrhythmic strategies in a setting of Torsades de Pointes (TdP) induction with a standard IKr inhibitor...
March 31, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28380257/tdp-43-and-fus-en-route-from-the-nucleus-to-the-cytoplasm
#14
REVIEW
Helena Ederle, Dorothee Dormann
Misfolded or mislocalized RNA-binding proteins (RBPs) and, consequently, altered mRNA processing, can cause neuronal dysfunction, eventually leading to neurodegeneration. Two prominent examples are the RBPs TDP-43 (TAR DNA binding protein of 43 kDa) and FUS (Fused in sarcoma), which form pathological mRNP aggregates in patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative disorders. Here, we review the multiple functions of TDP-43 and FUS in mRNA processing, both in the nucleus and in the cytoplasm...
April 5, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28379416/absence-of-alzheimer-disease-neuropathologic-changes-in-eyes-of-subjects-with-alzheimer-disease
#15
Erik A Williams, Declan McGuone, Matthew P Frosch, Bradley T Hyman, Nora Laver, Anat Stemmer-Rachamimov
Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features...
March 30, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28373710/single-cell-imaging-and-quantification-of-tdp-43-and-%C3%AE-synuclein-intercellular-propagation
#16
Sivan Peled, Dorin Sade, Yaron Bram, Ziv Porat, Topaz Kreiser, Michael Mimouni, Alexandra Lichtenstein, Daniel Segal, Ehud Gazit
The intercellular spreading of protein assemblies is a major factor in the progression of neurodegenerative disorders. The quantitative study and visualization of cell-to-cell propagation using tagged-proteins is challenging due to the steric effect of relatively large fluorescence tags and the risk of 'false positive' identification when analyzing these rare transmission events. Here, we established a cell culture model to characterize the cell-to-cell transmission of TAR DNA-binding protein and α-synuclein, involved in amyotrophic lateral sclerosis and Parkinson's disease, respectively, using the small nine amino acid influenza hemagglutinin tag...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28372328/blood-based-oligomeric-and-other-protein-variant-biomarkers-to-facilitate-pre-symptomatic-diagnosis-and-staging-of-alzheimer-s-disease
#17
Stephanie M Williams, Philip Schulz, Terrone L Rosenberry, Richard J Caselli, Michael R Sierks
Oligomeric forms of amyloid-β (Aβ), tau, and TDP-43 play important roles in Alzheimer's disease (AD), and therefore are promising biomarkers. We previously generated single chain antibody fragments (scFvs) that selectively bind disease-related variants of these proteins including A4, C6T, and E1, which bind different oligomeric Aβ variants; D11C, which binds oligomeric tau; and AD-TDP1 and AD-TDP2, which bind disease related TDP-43 variants. To determine the utility of these disease-related variants as early biomarkers, we first analyzed 11 human sera samples obtained ∼2 years prior to an initial mild cognitive impairment (MCI) diagnosis...
March 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28369538/structure-of-acid-deoxyribonuclease
#18
Armando Varela-Ramirez, Jan Abendroth, Adrian A Mejia, Isabelle Q Phan, Donald D Lorimer, Thomas E Edwards, Renato J Aguilera
Deoxyribonuclease II (DNase II) is also known as acid deoxyribonuclease because it has optimal activity at the low pH environment of lysosomes where it is typically found in higher eukaryotes. Interestingly, DNase II has also been identified in a few genera of bacteria and is believed to have arisen via horizontal transfer. Here, we demonstrate that recombinant Burkholderia thailandensis DNase II is highly active at low pH in the absence of divalent metal ions, similar to eukaryotic DNase II. The crystal structure of B...
March 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28367944/-original-article-tdp-43-in-the-skin-of-amyotrophic-lateral-sclerosis-patients
#19
Keisuke Abe, Takuya Ohkubo, Takanori Yokota
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. A common characteristic of ALS pathology is cytoplasmic inclusions primarily composed of transactive response DNA-binding protein of 43 kDa (TDP-43). Production of TDP-43 in the central nervous system is strictly regulated, but it is not known whether this is also true in the skin of ALS patients. We found a gradual but significant reduction in epidermal TDP-43 mRNA expression with illness progression in ALS patients with upper-limb onset...
2017: Journal of Medical and Dental Sciences
https://www.readbyqxmd.com/read/28359306/clinicians-adherence-to-clinical-practice-guidelines-for-cardiac-function-monitoring-during-antipsychotic-treatment-a-retrospective-report-on-434-patients-with-severe-mental-illness
#20
Mirko Manchia, Giorgio Firinu, Bernardo Carpiniello, Federica Pinna
BACKGROUND: Severe mental illness (SMI) has considerable excess morbidity and mortality, a proportion of which is explained by cardiovascular diseases, caused in part by antipsychotic (AP) induced QT-related arrhythmias and sudden death by Torsade de Point (TdP). The implementation of evidence-based recommendations for cardiac function monitoring might reduce the incidence of these AP-related adverse events. To investigate clinicians' adherence to cardiac function monitoring before and after starting AP, we performed a retrospective assessment of 434 AP-treated SMI patients longitudinally followed-up for 5 years at an academic community mental health center...
March 31, 2017: BMC Psychiatry
keyword
keyword
19782
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"