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https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#1
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28210980/molecular-mechanisms-of-ire1%C3%AE-ask1-pathway-reactions-to-unfolded-protein-response-in-drn-neurons-of-post-traumatic-stress-disorder-rats
#2
Fanzhen Kong, Fang Han, Yanhao Xu, Yuxiu Shi
The goal of this study was to further elucidate the molecular mechanisms of post-traumatic stress disorder (PTSD) pathogenesis and to provide experimental evidence for new drug targets for effective PTSD treatment. Expression changes of IRE1α, ASK1, and other downstream molecules of the IRE1α-ASK1 endoplasmic reticulum stress (ERS) signaling pathway were investigated. JNK, P38, CHOP, Bcl-2, and Bax were analyzed at both protein and mRNA levels of dorsal raphe nucleus (DRN) neurons of PTSD rats. The rat PTSD model was established via the single-prolonged stress (SPS) method...
February 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28208663/endoplasmic-reticulum-er-stress-and-endocrine-disorders
#3
REVIEW
Daisuke Ariyasu, Hiderou Yoshida, Yukihiro Hasegawa
The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the "unfolded protein response" (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207988/the-role-of-the-unfolded-protein-response-in-dengue-virus-pathogenesis
#4
REVIEW
Nilanka Perera, Joanna L Miller, Nicole Zitzmann
Symptomatic dengue virus (DENV) infections range from mild fever to severe haemorrhagic disease and death. Host-viral interactions play a significant role in deciding the fate of the infection. The unfolded protein response (UPR) is a pro-survival cellular reaction induced in response to DENV mediated ER stress. The UPR has complex interactions with the cellular autophagy machinery, apoptosis and innate immunity. DENV has evolved to manipulate the UPR to facilitate its replication and to evade host immunity...
February 16, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28205568/luman-contributes-to-brefeldin-a-induced-prion-protein-gene-expression-by-interacting-with-the-erse26-element
#5
Marc-André Déry, Andréa C LeBlanc
The cellular prion protein (PrP) is essential for transmissible prion diseases, but its exact physiological function remains unclear. Better understanding the regulation of the human prion protein gene (PRNP) expression can provide insight into this elusive function. Spliced XBP1 (sXBP1) was recently shown to mediate endoplasmic reticulum (ER) stress-induced PRNP expression. In this manuscript, we identify Luman, a ubiquitous, non-canonical unfolded protein response (UPR), as a novel regulator of ER stress-induced PRNP expression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#6
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202663/translating-protein-phosphatase-research-into-treatments-for-neurodegenerative-diseases
#7
REVIEW
Jeyapriya R Sundaram, Irene C J Lee, Shirish Shenolikar
Many of the major neurodegenerative disorders are characterized by the accumulation of intracellular protein aggregates in neurons and other cells in brain, suggesting that errors in protein quality control mechanisms associated with the aging process play a critical role in the onset and progression of disease. The increased understanding of the unfolded protein response (UPR) signaling network and, more specifically, the structure and function of eIF2α phosphatases has enabled the development or discovery of small molecule inhibitors that show great promise in restoring protein homeostasis and ameliorating neuronal damage and death...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202509/sodium-channel-subunit-scnn1b-suppresses-gastric-cancer-growth-and-metastasis-via-grp78-degradation
#8
Jun Yu, Qian Yun, Chi Chun Wong, Jiaying Xu, Huarong Chen, Yanquan Zhang, Wei Kang, Hua Wang, Li Zhang, Weilin Li, Eagle Sh Chu, Minnie Yy Go, Philip Wy Chiu, Enders Kw Ng, Francis Kl Chan, Joseph Jy Sung, Jianmin Si
There remains a paucity of functional biomarkers in gastric cancer. Here we report the identification of the sodium channel subunit SCNN1B as a candidate biomarker in gastric cancer (GC). SCNN1B mRNA expression was silenced commonly by promoter hypermethylation in GC cell lines and primary tumor tissues. Tissue microarray analysis revealed that high expression of SCNN1B was an independent prognostic factor for longer survival in GC patients, especially those with late-stage disease. Functional studies demonstrated that SCNN1B overexpression was sufficient to suppress multiple features of cancer cell pathophysiology in vitro and in vivo...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28193450/heat-shock-70%C3%A2-kda-protein-cognate-5-involved-in-wssv-toleration-of-litopenaeus-vannamei
#9
Kai Yuan, Feng-Hua Yuan, Hong-Hui He, Hai-Tao Bi, Shao-Ping Weng, Jian-Guo He, Yi-Hong Chen
The expression levels of 97 unigenes encoding heat shock proteins of Litopenaeus vannamei was scanned, and ten of them were significantly induced by white spot syndrome virus (WSSV). Among these genes, heat shock 70 kDa protein cognate 5 (LvHSC70-5) was upregulated to the highest extent and subjected to further studies. Subcellular localization assay revealed that LvHSC70-5 was located in the mitochondria. Aside from WSSV infection, unfolded protein response activation and thermal stress could also upregulate LvHSC70-5...
February 10, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28192116/prrt2-inhibits-the-proliferation-of-glioma-cells-by-modulating-unfolded-protein-response-pathway
#10
Guanghui Bi, Jingfeng Yan, Shuzhen Sun
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28186986/common-cytotoxic-chemotherapeutics-induce-epithelial-mesenchymal-transition-emt-downstream-of-er-stress
#11
Parag P Shah, Tess V Dupre, Leah J Siskind, Levi J Beverly
Endoplasmic reticulum (ER) in eukaryotes is a main organelle involved in a wide variety of functions including calcium storage, lipid biosynthesis, protein folding and protein transport. Disruption of ER homeostasis leads to ER stress and activation of the unfolded protein response (UPR). We and others have previously found that ER stress induces EMT in different cellular systems. Induction of ER stress with chemical modulators of ER homeostasis was sufficient to activate an EMT-like state in all cellular systems tested...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186786/nonlinear-loading-rate-dependent-force-response-of-individual-vimentin-intermediate-filaments-to-applied-strain
#12
Johanna Block, Hannes Witt, Andrea Candelli, Erwin J G Peterman, Gijs J L Wuite, Andreas Janshoff, Sarah Köster
The mechanical properties of eukaryotic cells are to a great extent determined by the cytoskeleton, a composite network of different filamentous proteins. Among these, intermediate filaments (IFs) are exceptional in their molecular architecture and mechanical properties. Here we directly record stress-strain curves of individual vimentin IFs using optical traps and atomic force microscopy. We find a strong loading rate dependence of the mechanical response, supporting the hypothesis that IFs could serve to protect eukaryotic cells from fast, large deformations...
January 27, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28184000/angptl6-expression-is-coupled-with-mitochondrial-oxphos-function-to-regulate-adipose-fgf21
#13
Seul Gi Kang, Hyon-Seung Yi, Min Jeong Choi, Min Jeong Ryu, Saetbyel Jung, Hyo Kyun Chung, Joon Young Chang, Yong Kyung Kim, Seong Eun Lee, Hyeon-Woo Kim, Hoil Choi, Dong Seok Kim, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Chul-Ho Lee, Yuichi Oike, Minho Shong
Recent studies revealed that the inhibition of mitochondrial oxidative phosphorylation (OXPHOS) is coupled with the mitochondrial unfolded protein response, thereby stimulating the secretion of non-cell-autonomous factors, which may control systemic energy metabolism and longevity. However, the nature and roles of non-cell-autonomous factors induced in adipose tissue in response to reduced OXPHOS function remain to be clarified in mammals. CR6-interacting factor 1 (CRIF1) is an essential mitoribosomal protein for the intramitochondrial production of mtDNA-encoded OXPHOS subunits...
February 9, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28180062/blocking-inos-and-endoplasmic-reticulum-stress-synergistically-improves-insulin-resistance-in-mice
#14
Tamires M Zanotto, Paula G F Quaresma, Dioze Guadagnini, Lais Weissmann, Andressa C Santos, Juliana F Vecina, Kelly Calisto, Andrey Santos, Patrícia O Prada, Mario J A Saad
OBJECTIVE: Recent data show that iNOS has an essential role in ER stress in obesity. However, whether iNOS is sufficient to account for obesity-induced ER stress and Unfolded Protein Response (UPR) has not yet been investigated. In the present study, we used iNOS knockout mice to investigate whether high-fat diet (HFD) can still induce residual ER stress-associated insulin resistance. METHODS: For this purpose, we used the intraperitoneal glucose tolerance test (GTT), euglycemic-hyperinsulinemic clamp, western blotting and qPCR in liver, muscle, and adipose tissue of iNOS KO and control mice on HFD...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28179109/mechanisms-of-defense-against-products-of-cysteine-catabolism-in-the-nematode-caenorhabditis-elegans
#15
Leonid Livshits, Arijit Kumar Chatterjee, Netanel Karbian, Rachel Abergel, Zohar Abergel, Einav Gross
Cysteine catabolism presents cells with a double-edged sword. On the one hand, cysteine degradation provides cells with essential molecules such as taurine and sulfide. The formation of sulfide in cells is thought to regulate important and diverse physiological processes including blood circulation, synaptic activity and inflammation. On the other hand, the catabolism of cysteine by gut microbiota can release high levels of sulfide that may underlie the development or relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide...
February 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28178654/hepatitis-b-virus-surface-proteins-accelerate-cholestatic-injury-and-tumor-progression-in-abcb4-knockout-mice
#16
Daniel Zahner, Hannah Glimm, Tomomitsu Matono, Yuri Churin, Diran Herebian, Ertan Mayatepek, Kernt Köhler, Stefan Gattenlöhner, Anne Stinn, Annette Tschuschner, Martin Roderfeld, Elke Roeb
: Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4-/- and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178232/synthetic-vulnerabilities-of-mesenchymal-subpopulations-in-pancreatic-cancer
#17
Giannicola Genovese, Alessandro Carugo, James Tepper, Frederick Scott Robinson, Liren Li, Maria Svelto, Luigi Nezi, Denise Corti, Rosalba Minelli, Piergiorgio Pettazzoni, Tony Gutschner, Chia-Chin Wu, Sahil Seth, Kadir Caner Akdemir, Elisabetta Leo, Samirkumar Amin, Marco Dal Molin, Haoqiang Ying, Lawrence N Kwong, Simona Colla, Koichi Takahashi, Papia Ghosh, Virginia Giuliani, Florian Muller, Prasenjit Dey, Shan Jiang, Jill Garvey, Chang-Gong Liu, Jianhua Zhang, Timothy P Heffernan, Carlo Toniatti, Jason B Fleming, Michael G Goggins, Laura D Wood, Alessandro Sgambato, Abbas Agaimy, Anirban Maitra, Charles W M Roberts, Huamin Wang, Andrea Viale, Ronald A DePinho, Giulio F Draetta, Lynda Chin
Malignant neoplasms evolve in response to changes in oncogenic signalling. Cancer cell plasticity in response to evolutionary pressures is fundamental to tumour progression and the development of therapeutic resistance. Here we determine the molecular and cellular mechanisms of cancer cell plasticity in a conditional oncogenic Kras mouse model of pancreatic ductal adenocarcinoma (PDAC), a malignancy that displays considerable phenotypic diversity and morphological heterogeneity. In this model, stochastic extinction of oncogenic Kras signalling and emergence of Kras-independent escaper populations (cells that acquire oncogenic properties) are associated with de-differentiation and aggressive biological behaviour...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28177775/cellular-stress-associated-with-plasmodium-berghei-ookinete-differentiation
#18
Josefina Duran-Bedolla, Juan Tellez-Sosa, Humberto Valdovinos-Torres, Natalia Pavon, Mabel Buelna-Chontal, Angel Tello-Lopez, Rocio Argotte-Ramos, Mario Henry Rodriguez, Maria Carmen Rodriguez
For malaria transmission, Plasmodium parasites must develop in the mosquito vector. Oxidative stress in the insect midgut, triggered by environmental changes (e.g., pH and temperature), influences the cellular signaling of parasites involved in differentiation from gametocytes to mobil ookinetes. It activates the homeostatic response to stress characterized by the phosphorylation eIF2, the attenuation of protein synthesis and the transcription of genes participating in the unfolded protein response and antioxidant processes, forming a part of an integrated stress response (ISR)...
August 12, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28177127/emerging-roles-of-er-stress-and-unfolded-protein-response-pathways-in-skeletal-muscle-health-and-disease
#19
REVIEW
Kyle R Bohnert, Joseph D McMillan, Ashok Kumar
Skeletal muscle is the most abundant tissue in the human body and can adapt its mass as a consequence of physical activity, metabolism, growth factors, and disease conditions. Skeletal muscle contains an extensive network of endoplasmic reticulum (ER), called sarcoplasmic reticulum, which plays an important role in the regulation of proteostasis and calcium homeostasis. In many cell types, environmental and genetic factors that disrupt ER function cause an accumulation of misfolded and unfolded proteins in the ER lumen that ultimately leads to ER stress...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28174720/netrin-1-protects-hepatocytes-against-cell-death-through-sustained-translation-during-the-unfolded-protein-response
#20
Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Maud Michelet, Benjamin Ducarouge, Alfredo Berzal-Herranz, Fabien Zoulim, Patrick Mehlen, Romain Parent
BACKGROUND & AIMS: Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptors deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR) triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
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