keyword
MENU ▼
Read by QxMD icon Read
search

TDP-43

keyword
https://www.readbyqxmd.com/read/28915616/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#1
Tzu-Wei Lin, Ming-Teh Chen, Liang-Ting Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912300/-18-f-av-1451-binding-in-vivo-mirrors-the-expected-distribution-of-tdp-43-pathology-in-the-semantic-variant-of-primary-progressive-aphasia
#2
W R Bevan-Jones, Thomas E Cope, P Simon Jones, Luca Passamonti, Young T Hong, Tim D Fryer, Robert Arnold, Kieren S J Allinson, Jonathan P Coles, Franklin I Aigbirhio, Karalyn Patterson, John T O'Brien, James B Rowe
INTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [(18)F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [(18)F]AV-1451...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28906030/pathological-and-immunoblot-analysis-of-phosphorylated-tdp-43-in-sporadic-amyotrophic-lateral-sclerosis-with-pallido-nigro-luysian-degeneration
#3
Akiko Uchino, Mieko Ogino, Junko Takahashi-Fujigasaki, Saori Oonuma, Naomi Kanazawa, Sabine Kajita, Masaaki Ichinoe, Masato Hasegawa, Kazutoshi Nishiyama, Shigeo Murayama
Transactivation response DNA-binding protein 43 kDa (TDP-43) is a key protein of sporadic amyotrophic lateral sclerosis (ALS), and phosphorylated form of TDP-43 (p-TDP-43) is a major pathological protein that accumulates in sporadic ALS. p-TDP-43 is found not only in primary motor neurons, but often propagates to non-motor systems as well. However, pallido-nigro-luysian (PNL) degeneration (PNLD) is rarely associated with ALS. We describe here a 68-year-old ALS patient presenting severe PNLD. He had difficulty walking due to poor movement of his right leg, and was diagnosed as having Parkinson's disease because of akinesia...
September 14, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28894122/onset-of-disorder-and-protein-aggregation-due-to-oxidation-induced-intermolecular-disulfide-bonds-case-study-of-rrm2-domain-from-tdp-43
#4
Sevastyan O Rabdano, Sergei A Izmailov, Dmitrii A Luzik, Adam Groves, Ivan S Podkorytov, Nikolai R Skrynnikov
We have investigated the behavior of second RNA-recognition motif (RRM2) of neuropathological protein TDP43 under the effect of oxidative stress as modeled in vitro. Toward this end we have used the specially adapted version of H/D exchange experiment, NMR relaxation and diffusion measurements, dynamic light scattering, controlled proteolysis, gel electrophoresis, site-directed mutagenesis and microsecond MD simulations. Under oxidizing conditions RRM2 forms disulfide-bonded dimers that experience unfolding and then assemble into aggregate particles (APs)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877758/neuron-loss-and-degeneration-in-the-progression-of-tdp-43-in-frontotemporal-lobar-degeneration
#5
Ahmed Yousef, John L Robinson, David J Irwin, Matthew D Byrne, Linda K Kwong, Edward B Lee, Yan Xu, Sharon X Xie, Lior Rennert, EunRan Suh, Vivianna M Van Deerlin, Murray Grossman, Virginia M-Y Lee, John Q Trojanowski
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases...
September 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28874134/amyotrophic-lateral-sclerosis-modifies-progenitor-neural-proliferation-in-adult-classic-neurogenic-brain-niches
#6
Lucía Galán, Ulises Gómez-Pinedo, Antonio Guerrero, Jose Manuel García-Verdugo, Jorge Matías-Guiu
BACKGROUND: Adult neurogenesis persists through life at least in classic neurogenic niches. Neurogenesis has been previously described as reduced in neurodegenerative diseases. There is not much knowledge about is adult neurogenesis is or not modified in amyotrophy lateral sclerosis (ALS). All previous publications has studied the ALS SOD1 (superoxide dismutase) transgenic mouse model. The purpose of this study is to examine the process of adult neurogenesis in classic niches (subventricular zone [SVZ] and subgranular zone [SGZ] of the dentate gyrus) in patients with amyotrophic lateral sclerosis (ALS), both with (ALS-FTD) and without associated frontotemporal dementia (FTD)...
September 6, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28872135/methods-and-tips-for-intravenous-administration-of-adeno-associated-virus-to-rats-and-evaluation-of-central-nervous-system-transduction
#7
Mychal S Grames, Kasey L Jackson, Robert D Dayton, John A Stanford, Ronald L Klein
Adeno-associated virus (AAV) vectors are a key reagent in the neurosciences for clustered regularly interspaced short palindromic repeats (CRISPR), optogenetics, cre-lox targeting, etc. The purpose of this manuscript is to aid the investigator attempting expansive central nervous system (CNS) gene transfer in the rat via tail vein injection of AAV. Wide-scale expression is relevant for conditions with widespread pathology, and a rat model is significant due to its greater size and physiologic similarities to humans compared to mice...
August 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28860970/failure-to-deliver-and-translate-new-insights-into-rna-dysregulation-in-als
#8
REVIEW
Alyssa N Coyne, Benjamin L Zaepfel, Daniela C Zarnescu
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28859339/pathologic-involvement-of-glutamatergic-striatal-inputs-from-the-cortices-in-tar-dna-binding-protein-43%C3%A2-kda-related-frontotemporal-lobar-degeneration-and-amyotrophic-lateral-sclerosis
#9
Yuichi Riku, Hirohisa Watanabe, Mari Yoshida, Maya Mimuro, Yasushi Iwasaki, Michihito Masuda, Shinsuke Ishigaki, Masahisa Katsuno, Gen Sobue
In frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), recent studies have presumed relationships between cognitive declines and striatal dysfunctions. The striatum contributes to socio-cognitive functions by receiving glutamatergic inputs from the cerebral cortices. However, the vulnerability of these cortico-striatal inputs is unclear in these diseases. This study aimed to evaluate the glutamatergic inputs to the striatum from the cerebral cortices in patients with sporadic TDP-43-related FTLD (FTLD-TDP) and ALS (ALS-TDP)...
September 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28859337/amygdala-tdp-43-pathology-in-frontotemporal-lobar-degeneration-and-motor-neuron-disease
#10
Takahiro Takeda, Danielle Seilhean, Isabelle Le Ber, Stéphanie Millecamps, Véronique Sazdovitch, Kazuo Kitagawa, Toshiki Uchihara, Charles Duyckaerts
TDP-43-positive inclusions are present in the amygdala in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) including amyotrophic lateral sclerosis. Behavioral abnormalities, one of the chief symptoms of FTLD, could be, at least partly, related to amygdala pathology. We examined TDP-43 inclusions in the amygdala of patients with sporadic FTLD/MND (sFTLD/MND), FTLD/MND with mutation of the C9ORF72 (FTLD/MND-C9) and FTLD with mutation of the progranulin (FTLD-GRN). TDP-43 inclusions were common in each one of these subtypes, which can otherwise be distinguished on topographical and genetic grounds...
September 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28854702/splicing-factors-act-as-genetic-modulators-of-tdp-43-production-in-a-new-autoregulatory-tdp-43-drosophila-model
#11
Marine Pons, Laetitia Miguel, Camille Miel, Tracey Avequin, François Juge, Thierry Frebourg, Dominique Campion, Magalie Lecourtois
TDP-43 is a critical RNA-binding factor associated with RNA metabolism. In the physiological state, maintaining normal TDP-43 protein levels is critical for proper physiological functions of the cells. As such, TDP-43 expression is tightly regulated through an autoregulatory negative feedback loop. TDP-43 is a major disease-causing protein in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). Several studies argue for a pathogenic role of elevated TDP-43 levels in these disorders...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28852778/pathogenic-mutation-in-the-als-ftd-gene-ccnf-causes-elevated-lys48-linked-ubiquitylation-and-defective-autophagy
#12
Albert Lee, Stephanie L Rayner, Serene S L Gwee, Alana De Luca, Hamideh Shahheydari, Vinod Sundaramoorthy, Audrey Ragagnin, Marco Morsch, Rowan Radford, Jasmin Galper, Sarah Freckleton, Bingyang Shi, Adam K Walker, Emily K Don, Nicholas J Cole, Shu Yang, Kelly L Williams, Justin J Yerbury, Ian P Blair, Julie D Atkin, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics, such as aberrant accumulation and ubiquitylation of TDP-43; however, the mechanisms that drive this process remain poorly understood. We have recently identified CCNF mutations in familial and sporadic ALS and FTD patients. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase (SCF(cyclin F)) complex that is responsible for ubiquitylating proteins for degradation by the ubiquitin-proteasome system...
August 29, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28845019/progranulin-haploinsufficiency-reduces-amyloid-beta-deposition-in-alzheimer-s-disease-model-mice
#13
Masato Hosokawa, Yoshinori Tanaka, Tetsuaki Arai, Hiromi Kondo, Haruhiko Akiyama, Masato Hasegawa
Granulin (Grn) mutations were identified in familial frontotemporal lobar degeneration (FTLD) patients with TDP-43 pathology. Grn transcript haploinsufficiency is proposed as a disease mechanism that leads to the loss of functional progranulin (PGRN) protein. Thus, these mutations are strongly involved in FTLD pathogenesis. Moreover, recent findings indicate that Grn mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer's disease. To investigate the influence of PGRN on amyloid beta (Aβ) accumulation, amyloid precursor protein (APP) transgenic mice were interbred with Grn-deficient mice, producing APP transgenic mice harboring the Grn hemizygote (APP/Grn(+/-))...
August 25, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28842427/quantitative-assessment-of-the-degradation-of-aggregated-tdp-43-mediated-by-the-ubiquitin-proteasome-system-and-macroautophagy
#14
Roberta Cascella, Giulia Fani, Claudia Capitini, Paola Rusmini, Angelo Poletti, Cristina Cecchi, Fabrizio Chiti
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43-associated disorders...
August 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28837687/the-spliceosome-associated-protein-mfap1-binds-to-vcp-in-drosophila
#15
Sandra Rode, Henrike Ohm, Jaqueline Zipfel, Sebastian Rumpf
Posttranscriptional regulation of gene expression contributes to many developmental transitions. Previously, we found that the AAA chaperone Valosin-Containing Protein (VCP) regulates ecdysone-dependent dendrite pruning of Drosophila class IV dendritic arborization (c4da) neurons via an effect on RNA metabolism. In a search for RNA binding proteins associated with VCP, we identified the spliceosome-associated protein Mfap1, a component of the tri-snRNP complex. Mfap1 is a nucleolar protein in neurons and its levels are regulated by VCP...
2017: PloS One
https://www.readbyqxmd.com/read/28835281/lysosomal-processing-of-progranulin
#16
Xiaolai Zhou, Daniel H Paushter, Tuancheng Feng, Lirong Sun, Thomas Reinheckel, Fenghua Hu
BACKGROUND: Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. PGRN is localized to the lysosome and important for proper lysosome function. However, the metabolism of PGRN in the lysosome is still unclear. RESULTS: Here, we report that PGRN is processed into ~10 kDa peptides intracellularly in multiple cell types and tissues and this processing is dependent on lysosomal activities...
August 23, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28833982/the-n-terminal-domain-of-als-linked-tdp-43-assembles-without-misfolding
#17
Phoebe S Tsoi, Kyoung-Jae Choi, Paul G Leonard, Antons Sizovs, Mahdi Muhammad Moosa, Kevin R MacKenzie, Josephine C Ferreon, Allan Chris M Ferreon
Transactivation response element (TAR) DNA-binding protein 43 (TDP-43) protein misfolding is implicated in several neurodegenerative diseases characterized by aggregated protein inclusions. Misfolding is believed to be mediated by both the N- and C-terminus of TDP-43; however, the mechanistic basis of the contribution of individual domains in the process remained elusive. Here, using single-molecule fluorescence and ensemble biophysical techniques, and a wide range of pH and temperature conditions, we show that TDP-43NTD is thermodynamically stable, well-folded and undergoes reversible oligomerization...
August 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28833898/hippocampal-sclerosis-hippocampal-neuron-loss-patterns-and-tdp-43-in-the-aged-population
#18
Suvi R K Hokkanen, Sally Hunter, Tuomo M Polvikoski, Hannah A D Keage, Thais Minett, Fiona E Matthews, Carol Brayne
Hippocampal neuron loss is a common neuropathological feature in old age with various underlying aetiologies. Hippocampal sclerosis of aging (HS-Aging) is neuropathologically characterized by severe CA1 neuronal loss and frequent presence of transactive response DNA-binding protein of 43kDa (TDP-43) aggregations. Its aetiology is unclear and currently no standardized approaches to measure HS-Aging exist. We developed a semi-quantitative protocol, which captures various hippocampal neuron loss patterns, and compared their occurrence in the context of HS-Aging, TDP-43, vascular and tau pathology in 672 brains (TDP-43 staining n=642/672, 96%) donated for the population-based Cambridge City over-75s Cohort and the Cognitive Function and Ageing Study...
August 18, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28832631/dna-strand-breaks-and-tdp-43-mislocation-are-absent-in-the-murine-hsod1g93a-model-of-amyotrophic-lateral-sclerosis-in-vivo-and-in-vitro
#19
Diane Penndorf, Vedrana Tadić, Otto W Witte, Julian Grosskreutz, Alexandra Kretz
Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g., organelle dysfunction, RNA metabolism and oxidative DNA damage conferred by SOD1 malfunction. However, apart from metabolically evoked DNA oxidation, it is unclear whether severe genotoxicity including DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), originates from loss of function of nuclear SOD1 enzyme. Factors that endogenously interfere with DNA integrity and repair complexes in hSOD1-mediated fALS remain similarly unexplored...
2017: PloS One
https://www.readbyqxmd.com/read/28831750/imbalanced-expression-of-polycistronic-mirna-in-acute-myeloid-leukemia
#20
Ryutaro Kotaki, Hiroshi Higuchi, Daisuke Ogiya, Yasuhiro Katahira, Natsumi Kurosaki, Naoko Yukihira, Jun Ogata, Haruna Yamamoto, Syakira Mohamad Alba, Azran Azhim, Tatsuo Kitajima, Shigeaki Inoue, Kazuhiro Morishita, Koh Ono, Ryo Koyama-Nasu, Ai Kotani
miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines...
August 22, 2017: International Journal of Hematology
keyword
keyword
15906
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"