keyword
MENU ▼
Read by QxMD icon Read
search

misfolding

keyword
https://www.readbyqxmd.com/read/29346549/transcriptome-and-functional-analysis-in-a-drosophila-model-of-ngly1-deficiency-provides-insight-into-therapeutic-approaches
#1
Katie G Owings, Joshua B Lowry, Yiling Bi, Matthew Might, Clement Y Chow
Autosomal recessive loss-of-function mutations in N-Glycanase 1 (NGLY1) cause NGLY1 deficiency, the only known human disease of deglycosylation. Patients present with developmental delay, movement disorder, seizures, liver dysfunction, and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD and other cellular processes and results in the constellation of problems associated with NGLY1 deficiency...
January 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29346421/the-absence-of-specific-yeast-heat-shock-proteins-leads-to-abnormal-aggregation-and-compromised-autophagic-clearance-of-mutant-huntingtin-proteins
#2
Ryan Higgins, Marie-Helene Kabbaj, Alexa Hatcher, Yanchang Wang
The functionality of a protein depends on its correct folding, but newly synthesized proteins are susceptible to aberrant folding and aggregation. Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat expansion in the Huntingtin gene (HTT) results in the expression of misfolded Huntingtin protein (Htt), which contributes to the development of Huntington's disease. We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy...
2018: PloS One
https://www.readbyqxmd.com/read/29345424/a-fluorescence-based-sensor-assay-that-monitors-general-protein-aggregation-in-human-cells
#3
Marisa Pereira, Diogo Tomé, Ana S Domingues, Ana S Varanda, Cristiana Paulo, Manuel A S Santos, Ana R Soares
Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27 for aggregated proteins can be explored to monitor aggregation in living cells by fusing it to a fluorescent protein as Green Fluorescent Protein (GFP)...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29343546/p62-filaments-capture-and-present-ubiquitinated-cargos-for-autophagy
#4
Gabriele Zaffagnini, Adriana Savova, Alberto Danieli, Julia Romanov, Shirley Tremel, Michael Ebner, Thomas Peterbauer, Martin Sztacho, Riccardo Trapannone, Abul K Tarafder, Carsten Sachse, Sascha Martens
The removal of misfolded, ubiquitinated proteins is an essential part of the protein quality control. The ubiquitin-proteasome system (UPS) and autophagy are two interconnected pathways that mediate the degradation of such proteins. During autophagy, ubiquitinated proteins are clustered in a p62-dependent manner and are subsequently engulfed by autophagosomes. However, the nature of the protein substrates targeted for autophagy is unclear. Here, we developed a reconstituted system using purified components and show that p62 and ubiquitinated proteins spontaneously coalesce into larger clusters...
January 17, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29342507/the-role-of-autophagy-in-the-degradation-of-misfolded-hla-b27-heavy-chains
#5
Fatemeh Navid, Gerlinde Layh-Schmitt, Keith A Sikora, Antony Cougnoux, Robert A Colbert
OBJECTIVE: To determine whether autophagy is involved in the degradation of misfolded HLA-B27 in experimental spondyloarthritis. METHODS: Bone marrow derived macrophages from HLA-B27 and human β2 m (hβ2 m) transgenic rats were examined with and without IFNγ and proteasome or autophagy inhibitors. Immunoprecipitation, western blotting, and immunofluorescence were used to measure HLA-B27 heavy chains and autophagy. Autophagy was induced using rapamycin. HLA-B7/hβ2 m transgenic and wild type rat macrophages were used as controls...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29342318/optical-structural-analysis-of-individual-%C3%AE-synuclein-oligomers
#6
Juan Alberto Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M Dobson, David Klenerman, Steven Lee
Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species are difficult to study due to the lack of methods capable of resolving these heterogeneous aggregates, which are smaller than the optical diffraction limit. We demonstrate here an all-optical fluorescence microscopy method to characterise the structure of individual protein-aggregates based on the fluorescence anisotropy of dyes such as thioflavin-T, and show that this technology is capable of studying oligomers in human biofluids such as cerebrospinal fluid...
January 17, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29339502/protein-aggregation-of-the-p63-transcription-factor-underlies-severe-skin-fragility-in-aec-syndrome
#7
Claudia Russo, Christian Osterburg, Anna Sirico, Dario Antonini, Raffaele Ambrosio, Julia Maren Würz, Jörg Rinnenthal, Marco Ferniani, Sebastian Kehrloesser, Birgit Schäfer, Peter Güntert, Satrajit Sinha, Volker Dötsch, Caterina Missero
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339327/the-chaperonin-cct-promotes-the-formation-of-fibrillar-aggregates-of-%C3%AE-tubulin
#8
Luis Pouchucq, Pablo Lobos-Ruiz, Gisela Araya, José María Valpuesta, Octavio Monasterio
The type II chaperonin CCT is involved in the prevention of the pathogenesis of numerous human misfolding disorders, as it sequesters misfolded proteins, blocks their aggregation and helps them to achieve their native state. In addition, it has been reported that CCT can prevent the toxicity of non-client amyloidogenic proteins by the induction of non-toxic aggregates, leading to new insight in chaperonin function as an aggregate remodeling factor. Here we add experimental evidence to this alternative mechanism by which CCT actively promotes the formation of conformationally different aggregates of γ-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-γ-tubulin interactions...
January 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29335505/perk-mediated-translational-control-is-required-for-collagen-secretion-in-chondrocytes
#9
Satoshi Hisanaga, Masato Miyake, Shusuke Taniuchi, Miho Oyadomari, Masatoshi Morimoto, Ryosuke Sato, Jun Hirose, Hiroshi Mizuta, Seiichi Oyadomari
As chondrocytes are highly secretory and they experience a variety of stresses, physiological unfolded protein response (UPR) signalling is essential for extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of the UPR pathway, PERK governs the translational attenuation and transcriptional upregulation of amino acid and redox metabolism and induction of apoptosis. It was previously demonstrated that a defect of the PERK branch of the UPR signalling pathway causes the accumulation of unfolded proteins, leading to cell death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in pancreatic β cells...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335442/nanostructural-differentiation-and-toxicity-of-amyloid-%C3%AE-25-35-aggregates-ensue-from-distinct-secondary-conformation
#10
Yongxiu Song, Ping Li, Lei Liu, Christian Bortolini, Mingdong Dong
Amyloid nanostructures are originated from protein misfolding and aberrant aggregation, which is associated with the pathogenesis of many types of degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The secondary conformation of peptides is of a fundamental importance for aggregation and toxicity of amyloid peptides. In this work, Aβ25-35, a fragment of amyloid β(1-42) (Aβ42), was selected to investigate the correlation between secondary structures and toxicity of amyloid fibrils...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331980/dmc1-mutation-that-causes-human-non-obstructive-azoospermia-and-premature-ovarian-insufficiency-identified-by-whole-exome-sequencing
#11
Wen-Bin He, Chao-Feng Tu, Qiang Liu, Lan-Lan Meng, Shi-Min Yuan, Ai-Xiang Luo, Fu-Sheng He, Juan Shen, Wen Li, Juan Du, Chang-Gao Zhong, Guang-Xiu Lu, Ge Lin, Li-Qing Fan, Yue-Qiu Tan
BACKGROUND: The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. METHODS: We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family...
January 13, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29331484/novel-biomolecular-information-in-rotenone-induced-cellular-model-of-parkinson-s-disease
#12
D Lin, Y Liang, D Zheng, Y Chen, X Jing, M Lei, Z Zeng, T Zhou, X Wu, S Peng, K Huang, L Yang, S Xiao, J Liu, E Tao
In order to uncover the remarkable pathogenic genes or molecular pathological process in Parkinson's disease (PD), we employed a microarray analysis upon the cellular PD model induced by rotenone. Compared to the control group, 2174 genes were screened out to be expressed differently in the rotenone-induced group by certain criterion. GO analysis and the pathways analysis showed the significant enrichment of genes that were associated with the biological process of cell cycle, apoptotic process, organelle fusion, mitochondrial lesion, endoplasmic reticulum stress and so on...
January 10, 2018: Gene
https://www.readbyqxmd.com/read/29331396/autophagy-in-ischemic-stroke
#13
REVIEW
Pei Wang, Bo-Zong Shao, Zhiqiang Deng, Shi Chen, Zhenyu Yue, Chao-Yu Miao
Autophagy is a self-eating cellular catabolic pathway, through which long-lived proteins, damaged organelles and misfolded proteins are degraded and recycled for the maintenance of cellular homeostasis and normal cellular functions. Autophagy plays an important homeostatic role in the regulation of cell survival. Accumulating evidence shows that autophagy is activated in various cell types in the brain such as neurons, glia cells, and brain microvascular cells upon ischemic stroke. However, the exact role and molecular mechanisms of autophagy process that is implicated in ischemic stroke have yet to be elucidated...
January 10, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29331378/loss-of-zebrafish-smyd1a-interferes-with-myofibrillar-integrity-without-triggering-the-misfolded-myosin-response
#14
Christoph Paone, Steven Rudeck, Christelle Etard, Uwe Strähle, Wolfgang Rottbauer, Steffen Just
Sarcomeric protein turnover needs to be tightly balanced to assure proper assembly and renewal of sarcomeric units within muscle tissues. The mechanisms regulating these fundamental processes are only poorly understood, but of great clinical importance since many cardiac and skeletal muscle diseases are associated with defective sarcomeric organization. The SET- and MYND domain containing protein 1b (Smyd1b) is known to play a crucial role in myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b and Hsp90α1...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330304/efficient-prion-disease-transmission-through-common-environmental-materials
#15
Sandra Pritzkow, Rodrigo Morales, Adam Lyon, Luis Concha-Marambio, Akihiko Urayama, Claudio Soto
Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials (i...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29325094/functional-rescue-of-misfolding-abca3-mutations-by-small-molecular-correctors
#16
Susanna Kinting, Stefanie Höppner, Ulrike Schindlbeck, Maria E Forstner, Jacqueline Harfst, Thomas Wittmann, Matthias Griese
ABCA3, a phospholipid transporter in lung lamellar bodies (LB), is essential for the assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure.The aim of this study was to prove that disease causing misfolding ABCA3 mutations can be corrected in vitro and to investigate available options for correction.We stably expressed HA-tagged wild type ABCA3 or variants p...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29324748/trans10-cis12-conjugated-linoleic-acid-inhibits-proliferation-and-migration-of-ovarian-cancer-cells-by-inducing-er-stress-autophagy-and-modulation-of-src
#17
Mian M K Shahzad, Mildred Felder, Kai Ludwig, Hannah R Van Galder, Matthew L Anderson, Jong Kim, Mark E Cook, Arvinder K Kapur, Manish S Patankar
The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM™ chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC50, 7 μM) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780...
2018: PloS One
https://www.readbyqxmd.com/read/29323786/pulmonary-endoplasmic-reticulum-stress-scars-smoke-and-suffocation
#18
REVIEW
Jennifer A Dickens, Elke Malzer, Joseph E Chambers, Stefan J Marciniak
Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic cases of pulmonary fibrosis appear to be strongly associated with activation of the unfolded protein response (UPR) and/or the integrated stress response (ISR). Inhalation of smoke can impair protein folding and may be an important cause of pulmonary ER stress...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29323280/nucleotide-exchange-factors-fes1-and-hspbp1-mimic-substrate-to-release-misfolded-proteins-from-hsp70
#19
Naveen K C Gowda, Jayasankar M Kaimal, Roman Kityk, Chammiran Daniel, Jobst Liebau, Marie Öhman, Matthias P Mayer, Claes Andréasson
Protein quality control depends on the tight regulation of interactions between molecular chaperones and polypeptide substrates. Substrate release from the chaperone Hsp70 is triggered by nucleotide-exchange factors (NEFs) that control folding and degradation fates via poorly understood mechanisms. We found that the armadillo-type NEFs budding yeast Fes1 and its human homolog HspBP1 employ flexible N-terminal release domains (RDs) with substrate-mimicking properties to ensure the efficient release of persistent substrates from Hsp70...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29322248/a-reversible-liquid-drop-aggregation-controls-glucose-response-in-yeast
#20
REVIEW
Kobi Simpson-Lavy, Martin Kupiec
Glucose is the preferred carbon of the yeast Saccharomyces cerevisiae. Depletion of glucose activates SNF1 (yeast AMP-activated protein kinase-AMPK), allowing cells to switch from fermentation to respiration. We have recently characterized the mechanism by which SNF1 activity is regulated by the Std1 protein, and its regulator Sip5. The hitherto uncharacterized protein kinase Vhs1 phosphorylates Sip5 in response to glucose availability, disengaging it from Std1 and promoting the sequestering of the SNF1 activator out of the nucleus into cytoplasmic puncta...
January 10, 2018: Current Genetics
keyword
keyword
38813
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"