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https://www.readbyqxmd.com/read/28106854/the-effect-of-polyphenols-on-protein-degradation-pathways-implications-for-neuroprotection
#1
REVIEW
Parvana Hajieva
Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106827/neuroprotective-strategy-in-retinal-degeneration-suppressing-er-stress-induced-cell-death-via-inhibition-of-the-mtor-signal
#2
REVIEW
Bin Fan, Ying-Jian Sun, Shu-Yan Liu, Lin Che, Guang-Yu Li
The retina is a specialized sensory organ, which is essential for light detection and visual formation in the human eye. Inherited retinal degenerations are a heterogeneous group of eye diseases that can eventually cause permanent vision loss. UPR (unfolded protein response) and ER (endoplasmic reticulum) stress plays an important role in the pathological mechanism of retinal degenerative diseases. mTOR (the mammalian target of rapamycin) kinase, as a signaling hub, controls many cellular processes, covering protein synthesis, RNA translation, ER stress, and apoptosis...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106068/alzheimer-disease-misfolded-diabetes-mellitus-peptide-seeds-amyloid-%C3%AE-aggregation
#3
Charlotte Ridler
No abstract text is available yet for this article.
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28104914/docosahexaenoic-acid-mediated-protein-aggregates-may-reduce-proteasome-activity-and-delay-myotube-degradation-during-muscle-atrophy-in-vitro
#4
Seung Kyun Shin, Ji Hyeon Kim, Jung Hoon Lee, Young Hoon Son, Min Wook Lee, Hak Joong Kim, Sue Ah Noh, Kwang Pyo Kim, In-Gyu Kim, Min Jae Lee
Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104575/modulation-of-proteostasis-by-transcription-factor-nrf2-and-impact-in-neurodegenerative-diseases
#5
REVIEW
Marta Pajares, Antonio Cuadrado, Ana I Rojo
Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2)...
January 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28103898/the-burden-of-amyloid-light-chain-amyloidosis-on-health-related-quality-of-life
#6
Martha Bayliss, Kristen L McCausland, Spencer D Guthrie, Michelle K White
BACKGROUND: Light chain (AL) amyloidosis is a rare disease characterized by misfolded amyloid protein deposits in tissues and vital organs, and little is known about the burden of AL amyloidosis on health-related quality of life. This study aimed to quantify the burden of AL amyloidosis in terms of health-related quality of life in a diverse, community-based sample of AL amyloidosis patients. RESULTS: The SF-36v2® Health Survey (SF-36v2), a widely used generic measure of health-related quality of life (using physical and mental summary scales and subscales assessing eight aspects of functioning and well-being), was administered as an online survey of AL amyloidosis patients with AL amyloidosis (ClinicalTrials...
January 19, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28102469/lanosterol-suppresses-the-aggregation-and-cytotoxicity-of-misfolded-proteins-linked-with-neurodegenerative-diseases
#7
Arun Upadhyay, Ayeman Amanullah, Ribhav Mishra, Amit Kumar, Amit Mishra
Accumulation of misfolded or aberrant proteins in neuronal cells is linked with neurodegeneration and other pathologies. Which molecular mechanisms fail and cause inappropriate folding of proteins and what is their relationship to cellular toxicity is not well known. How does it happen and what are the probable therapeutic or molecular approaches to counter them are also not clear. Here, we demonstrate that treatment of lanosterol diminishes aberrant proteotoxic aggregation and mitigates their cytotoxicity via induced expression of co-chaperone CHIP and elevated autophagy...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28102071/temperature-induced-misfolding-in-prion-protein-evidences-of-multiple-partially-disordered-states-stabilized-by-non-native-hydrogen-bonds
#8
Neharika G Chamachi, Suman Chakrabarty
The structural basis of misfolding pathways of a cellular Prion (PrP(C)) into the toxic scrapie form (PrP(SC)) and identification of possible intermediates (e.g. PrP(*)) still eludes us. In this work, we have used a cumulative ~65µs of Replica Exchange Molecular Dynamics simulation data to construct the conformational free energy landscapes and capture the structural and thermodynamic characteristics associated with various stages of the thermal denaturation process in human Prion protein. The temperature dependent free energy surfaces consist of multiple metastable states stabilized by non-native contacts and hydrogen bonds, thus rendering the protein prone towards misfolding...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28100837/erad-icating-mutant-insulin-promotes-functional-insulin-secretion
#9
Daniel J Moore
Overexpression of a chaperone protein liberates functional insulin from a misfolded mutant partner to improve insulin secretion.
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100635/phospholipase-lpl1-links-lipid-droplet-function-with-quality-control-protein-degradation
#10
Nina Weisshaar, Hendrik Welsch, Angel Guerra-Moreno, John Hanna
Protein misfolding is toxic to cells and is thought to underlie many human diseases, including many neurodegenerative diseases. Accordingly, cells have developed stress responses to deal with misfolded proteins. The transcription factor Rpn4 mediates one such response, and is best known for regulating the abundance of the proteasome, the complex multisubunit protease that destroys proteins. Here we identify Lpl1 as an unexpected target of the Rpn4 response. Lpl1 is a phospholipase and a component of the lipid droplet...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#11
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28096448/loss-of-function-mutations-in-hspr-rescue-the-growth-defect-of-a-mycobacterium-tuberculosis-proteasome-activator-e-pafe-mutant
#12
Jordan B Jastrab, Marie I Samanovic, Richard Copin, Bo Shopsin, K Heran Darwin
: Mycobacterium tuberculosis uses a proteasome to degrade proteins by both ATP-dependent and -independent pathways. While much has been learned about ATP-dependent degradation, relatively little is understood about the ATP-independent pathway, which is controlled by Mycobacterium tuberculosis proteasome accessory factor E (PafE). Recently, we found that a Mycobacterium tuberculosis pafE mutant has slowed growth in vitro and is sensitive to killing by heat stress. However, we did not know if these phenotypes were caused by an inability to degrade the PafE-proteasome substrate HspR (heat shock protein repressor), an inability to degrade any damaged or misfolded proteins, or a defect in another protein quality control pathway...
January 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28096357/prion-replication-without-host-adaptation-during-interspecies-transmissions
#13
Jifeng Bian, Vadim Khaychuk, Rachel C Angers, Natalia Fernández-Borges, Enric Vidal, Crystal Meyerett-Reid, Sehun Kim, Carla L Calvi, Jason C Bartz, Edward A Hoover, Umberto Agrimi, Jürgen A Richt, Joaquín Castilla, Glenn C Telling
Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrP(C)) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrP(C) Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrP(C) conversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096332/human-nf-%C3%AE%C2%BAb-repressing-factor-acts-as-a-stress-regulated-switch-for-ribosomal-rna-processing-and-nucleolar-homeostasis-surveillance
#14
Marta Coccia, Antonio Rossi, Anna Riccio, Edoardo Trotta, Maria Gabriella Santoro
The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096265/prion-properties-of-sod1-in-amyotrophic-lateral-sclerosis-and-potential-therapy
#15
Caroline Sibilla, Anne Bertolotti
Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressive neurodegenerative disease caused by the deterioration of motor neurons. The first symptoms of ALS always begin at a focal but variable site and consistently spread to neighboring regions, suggesting that neurodegeneration in ALS is an orderly and propagating process. Like other neurodegenerative diseases, misfolding of a specific protein is central to ALS. SOD1, the major constituent of the protein deposits in some familial and sporadic forms of ALS, propagates its misfolded conformation like prions, providing a plausible molecular basis for the focality and spreading of muscle weakness in ALS...
January 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28095319/autophagy-and-autoimmunity
#16
REVIEW
Dennis J Wu, Iannis E Adamopoulos
Autophagy is a highly conserved protein degradation pathway from yeasts to humans that is essential for removing protein aggregates and misfolded proteins in healthy cells. Recently, autophagy-related genes polymorphisms have been implicated in several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis. Numerous studies reveal autophagy and autophagy-related proteins also participate in immune regulation. Conditional deletions of autophagy-related proteins in mice have rendered protection from experimental autoimmune encephalomyelitis, and TNF-mediated joint destruction in animal models of multiple sclerosis and experimental arthritis respectively...
January 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28093972/conformation-as-the-therapeutic-target-for-neurodegenerative-diseases
#17
Rajaraman Krishnan, Franz Hefti, Haim Tsubery, Michal Lulu, Ming Proschitsky, Richard Fisher
Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets...
January 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28093848/one-mutation-two-distinct-disease-variants-unravelling-the-impact-of-transthyretin-amyloid-fibril-composition
#18
REVIEW
O B Suhr, E Lundgren, P Westermark
Although hereditary transthyretin (h-ATTR) amyloidosis is a monogenetic disease, a large variation in its phenotype has been observed. The common hypothesis of amyloid fibril formation involves dissociation of the transthyretin (TTR) tetramer into monomers that after misfolding reassemble into amyloid fibrils. This notion is partly challenged by the finding of two distinct types of amyloid fibrils. One of these, type A, consists of C-terminal ATTR fragments and full-length TTR, whereas the other, type B, consists only of full-length TTR...
January 17, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28091941/occurrence-of-complex-type-free-n-glycans-with-a-single-glcnac-residue-at-the-reducing-termini-in-the-fresh-water-plant-egeria-densa
#19
Megumi Maeda, Natsuki Ebara, Misato Tani, Christopher J Vavricka, Yoshinobu Kimura
In our previous study, we found unique free N-glycans (FNGs), which carry a single GlcNAc residue (GN1) at the reducing-end side and the Lewis-a epitope at the non-reducing-end side, in the culture broth of rice cells. Based on the FNG structural features and the substrate specificity of plant ENGase, we hypothesized that there might be a novel biosynthetic mechanism responsible for the production of these unique GN1-FNGs, in which high-mannose type (HMT)-GN1-FNGs produced in the cytosol from misfolded glycoproteins by ENGase are transported back into the endoplasmic reticulum and processed to plant complex type (PCT)-GN1-FNGs in the Golgi apparatus...
January 14, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28091582/androgen-mediated-regulation-of-endoplasmic-reticulum-associated-degradation-and-its-effects-on-prostate-cancer
#20
Yalcin Erzurumlu, Petek Ballar
The endoplasmic reticulum (ER) comprises thirty percent of the newly translated proteins in eukaryotic cells. The quality control mechanism within the ER distinguishes between properly and improperly folded proteins and ensures that unwanted proteins are retained in the ER and subsequently degraded through ER-associated degradation (ERAD). Besides cleaning of misfolded proteins ERAD is also important for physiological processes by regulating the abundance of normal proteins of the ER. Thus it is important to unreveal the regulation patterns of ERAD...
January 16, 2017: Scientific Reports
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