keyword
MENU ▼
Read by QxMD icon Read
search

Tdp 43

keyword
https://www.readbyqxmd.com/read/28724966/acetylation-induced-tdp-43-pathology-is-suppressed-by-an-hsf1-dependent-chaperone-program
#1
Ping Wang, Connor M Wander, Chao-Xing Yuan, Michael S Bereman, Todd J Cohen
TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28719018/ante-mortem-csf-tau-levels-correlate-with-post-mortem-tau-pathology-in-ftld
#2
D J Irwin, A Lleó, S X Xie, C T McMillan, D Wolk, E B Lee, V M Van Deerlin, L M Shaw, J Q Trojanowski, M Grossman
OBJECTIVE: To test the hypotheses that 1) antemortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration and 2) tauopathy patients have higher phosphorylated-tau levels compared to TDP-43 proteinopathy patients while accounting for Alzheimer's disease co-pathology. METHODS: Patients had autopsy-confirmed frontotemporal lobar degeneration with tauopathy (n=31), TDP-43 proteinopathy (n=49), or Alzheimer's disease (n=26) with antemortem cerebrospinal fluid...
July 18, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28711596/the-relevance-of-contact-independent-cell-to-cell-transfer-of-tdp-43-and-sod1-in-amyotrophic-lateral-sclerosis
#3
REVIEW
Maya A Hanspal, Christopher M Dobson, Justin J Yerbury, Janet R Kumita
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the formation of cytoplasmic aggregates by proteins including TDP-43 and SOD1, in affected cells in the central nervous system (CNS). Pathology spreads from an initial site of onset to contiguous anatomical regions. There is evidence that for disease-associated proteins, including TDP-43 and SOD1, non-native protein conformers can promote misfolding of the natively folded counterparts, and cell-to-cell transfer of pathological aggregates may underlie the spread of the disease throughout the CNS...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28710326/cortical-influences-drive-amyotrophic-lateral-sclerosis
#4
REVIEW
Andrew Eisen, Heiko Braak, Kelly Del Tredici, Roger Lemon, Albert C Ludolph, Matthew C Kiernan
The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS...
July 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28708134/neurodegenerative-disease-loss-of-tdp-43-in-microglia-friend-or-foe
#5
Charlotte Ridler
No abstract text is available yet for this article.
July 14, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28705014/mutation-in-the-rrm2-domain-of-tdp-43-in-amyotrophic-lateral-sclerosis-with-rapid-progression-associated-with-ubiquitin-positive-aggregates-in-cultured-motor-neurons
#6
Cindy Maurel, Blandine Madji-Hounoum, Rose-Anne Thepault, Sylviane Marouillat, Céline Brulard, Véronique Danel-Brunaud, Jean-Philippe Camdessanche, Helene Blasco, Philippe Corcia, Christian R Andres, Patrick Vourc'h
Mutations in the TAR-DNA Binding Protein-43 (TDP-43) encoding the TARDBP gene are present in amyotrophic lateral sclerosis (ALS). TDP-43 is the major component of ubiquitin-positive inclusions in motor neurons in ALS patients. We report here a novel heterozygous missense mutation in TARDBP in an ALS patient presenting a rapid form of ALS. This mutation p.N259S is located within the RNA recognition motif 2 (RRM2) in very close proximity with nucleotides in RNA. It is the first time a mutation was reported in this RRM2 domain of TDP-43...
July 13, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28701108/repetitive-mild-closed-head-injury-alters-protein-expression-and-dendritic-complexity-in-a-mouse-model
#7
Jessica Nicole Saykally, Whitney A Ratliff, Kristen Keeley, Chaim G Pick, Ronald F Mervis, Bruce A Citron
World-wide head injuries are a growing problem. In the United States alone, 1.7 million people suffer a head injury each year. While most of these injuries are mild, head injury sufferers still sustain symptoms that can have major medical and economical impacts. Moreover, repetitive mild head injuries, like those observed in active military personnel and athletes, have demonstrated a more severe and long-term set of consequences. In an effort to better understand the delayed pathological changes following multiple mild head injuries, we used a mouse model of mild closed head injury (with no motor deficits observed by rotarod testing) and measured dendritic complexity at 30 days after injury and potentially related factors up to 60 days post injury...
July 12, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28687523/tdp-43-in-the-spectrum-of-mnd-ftld-pathologies
#8
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/28686708/drosophila-lines-with-mutant-and-wild-type-human-tdp-43-replacing-the-endogenous-gene-reveals-phosphorylation-and-ubiquitination-in-mutant-lines-in-the-absence-of-viability-or-lifespan-defects
#9
Jer-Cherng Chang, David B Morton
Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines...
2017: PloS One
https://www.readbyqxmd.com/read/28674990/traumatic-brain-injury-as-a-trigger-of-neurodegeneration
#10
Victoria E Johnson, William Stewart, John D Arena, Douglas H Smith
Although millions of individuals suffer a traumatic brain injury (TBI) worldwide each year, it is only recently that TBI has been recognized as a major public health problem. Beyond the acute clinical manifestations, there is growing recognition that a single severe TBI (sTBI) or repeated mild TBIs (rTBI) can also induce insidious neurodegenerative processes, which may be associated with early dementia, in particular chronic traumatic encephalopathy (CTE). Identified at autopsy examination in individuals with histories of exposure to sTBI or rTBI, CTE is recognized as a complex pathology featuring both macroscopic and microscopic abnormalities...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28669544/tdp-43-depletion-in-microglia-promotes-amyloid-clearance-but-also-induces-synapse-loss
#11
Rosa C Paolicelli, Ali Jawaid, Christopher M Henstridge, Andrea Valeri, Mario Merlini, John L Robinson, Edward B Lee, Jamie Rose, Stanley Appel, Virginia M-Y Lee, John Q Trojanowski, Tara Spires-Jones, Paul E Schulz, Lawrence Rajendran
Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer's disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28666471/heterogeneous-ribonuclear-protein-e2-hnrnp-e2-is-associated-with-tdp-43-immunoreactive-neurites-in-semantic-dementia-but-not-with-other-tdp-43-pathological-subtypes-of-frontotemporal-lobar-degeneration
#12
Yvonne S Davidson, Andrew C Robinson, Louis Flood, Sara Rollinson, Bridget C Benson, Yasmine T Asi, Anna Richardson, Matthew Jones, Julie S Snowden, Stuart Pickering-Brown, Tammaryn Lashley, David M A Mann
Frontotemporal Lobar Degeneration (FTLD) encompasses certain related neurodegenerative disorders which alter personality and cognition. Heterogeneous ribonuclear proteins (hnRNPs) maintain RNA metabolism and changes in their function may underpin the pathogenesis of FTLD. Immunostaining for hnRNP E2 was performed on sections of frontal and temporal cortex with hippocampus from 80 patients with FTLD, stratified by pathology into FTLD-tau and FTLD-TDP type A, B and C subtypes, and by genetics into patients with C9orf72 expansions, MAPT or GRN mutations, or those with no known mutation, and on 10 healthy controls...
June 30, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28663553/functional-and-dynamic-polymerization-of-the-als-linked-protein-tdp-43-antagonizes-its-pathologic-aggregation
#13
Tariq Afroz, Eva-Maria Hock, Patrick Ernst, Chiara Foglieni, Melanie Jambeau, Larissa A B Gilhespy, Florent Laferriere, Zuzanna Maniecka, Andreas Plückthun, Peer Mittl, Paolo Paganetti, Frédéric H T Allain, Magdalini Polymenidou
TDP-43 is a primarily nuclear RNA-binding protein, whose abnormal phosphorylation and cytoplasmic aggregation characterizes affected neurons in patients with amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that physiological nuclear TDP-43 in mouse and human brain forms homo-oligomers that are resistant to cellular stress. Physiological TDP-43 oligomerization is mediated by its N-terminal domain, which can adopt dynamic, solenoid-like structures, as revealed by a 2.1 Å crystal structure in combination with nuclear magnetic resonance spectroscopy and electron microscopy...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28657719/nanoscale-analysis-reveals-the-maturation-of-neurodegeneration-associated-protein-aggregates-grown-in-mrna-granules-then-released-by-stress-granule-proteins
#14
Sanae Abrakhi, Dmitry A Kretov, Bénédicte Desforges, Ioana Dobra, Ahmed Bouhss, David Pastre, Loic Hamon
TDP-43 and FUS are two mRNA binding proteins associated to neurodegenerative diseases that form cytoplasmic inclusions with prion-like properties in affected neurons. Documenting the early stages of the formation of TDP-43 or FUS protein aggregates and the role of mRNA stress granules that are considered as critical intermediates for protein aggregation is therefore of interest to understand disease propagation. Here, we developed a single molecule approach via atomic force microscopy (AFM), which provides structural information out of reach by fluorescence microscopy...
June 28, 2017: ACS Nano
https://www.readbyqxmd.com/read/28653830/photocontrollable-probe-spatiotemporally-induces-neurotoxic-fibrillar-aggregates-and-impairs-nucleocytoplasmic-trafficking
#15
Ruei-Yu He, Shu-Han Chao, Yu-Ju Tsai, Chi-Chang Lee, Chu-Yi Yu, Hua-De Gao, Yung-An Huang, Eric Hwang, Hsien-Ming Lee, Joseph Jen-Tse Huang
The abnormal assembly of misfolded proteins into neurotoxic aggregates is the hallmark associated with neurodegenerative diseases. Herein, we establish a photocontrollable platform to trigger amyloidogenesis to recapitulate the pathogenesis of amyotrophic lateral sclerosis (ALS) by applying a chemically engineered probe as a "switch" in live cells. This probe is composed of an amyloidogenic peptide from TDP-43, a photolabile linker, a polycationic sequence both to mask amyloidogenicity and for cell penetration, and a fluorophore for visualization...
June 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28637276/repetitive-element-transcripts-are-elevated-in-the-brain-of-c9orf72-als-ftld-patients
#16
Mercedes Prudencio, Patrick K Gonzales, Casey N Cook, Tania F Gendron, Lillian M Daughrity, Yuping Song, Mark T W Ebbert, Marka van Blitterswijk, Yong-Jie Zhang, Karen Jansen-West, Matthew C Baker, Michael DeTure, Rosa Rademakers, Kevin B Boylan, Dennis W Dickson, Leonard Petrucelli, Christopher D Link
Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analyzed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls...
June 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28633435/mcm3ap-in-recessive-charcot-marie-tooth-neuropathy-and-mild-intellectual-disability
#17
Emil Ylikallio, Rosa Woldegebriel, Manuela Tumiati, Pirjo Isohanni, Monique M Ryan, Zornitza Stark, Maie Walsh, Sarah L Sawyer, Katrina M Bell, Alicia Oshlack, Paul J Lockhart, Mariia Shcherbii, Alejandro Estrada-Cuzcano, Derek Atkinson, Taila Hartley, Martine Tetreault, Inge Cuppen, W Ludo van der Pol, Ayse Candayan, Esra Battaloglu, Yesim Parman, Koen L I van Gassen, Marie-José H van den Boogaard, Kym M Boycott, Liisa Kauppi, Albena Jordanova, Tuula Lönnqvist, Henna Tyynismaa
Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function...
June 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28625595/dctn1-related-neurodegeneration-perry-syndrome-and-beyond
#18
REVIEW
Takuya Konno, Owen A Ross, Hélio A G Teive, Jarosław Sławek, Dennis W Dickson, Zbigniew K Wszolek
Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150(Glued). Dynactin is a motor protein involved in axonal transport; the p150(Glued) subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought...
June 12, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28625517/reduced-tdp-43-expression-improves-neuronal-activities-in-a-drosophila-model-of-perry-syndrome
#19
Yuka Hosaka, Tsuyoshi Inoshita, Kahori Shiba-Fukushima, Changxu Cui, Taku Arano, Yuzuru Imai, Nobutaka Hattori
Parkinsonian Perry syndrome, involving mutations in the dynein motor component dynactin or p150(Glued), is characterized by TDP-43 pathology in affected brain regions, including the substantia nigra. However, the molecular relationship between p150(Glued) and TDP-43 is largely unknown. Here, we report that a reduction in TDP-43 protein levels alleviates the synaptic defects of neurons expressing the Perry mutant p150(G50R) in Drosophila. Dopaminergic expression of p150(G50R), which decreases dopamine release, disrupts motor ability and reduces the lifespan of Drosophila...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#20
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
keyword
keyword
2568
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"