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https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#1
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926857/a-lon-clpp-proteolytic-axis-degrades-complex-i-to-extinguish-ros-production-in-depolarized-mitochondria
#2
Kenneth Robert Pryde, Jan Willem Taanman, Anthony Henry Schapira
Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson's disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#3
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27925697/prevalence-of-sj%C3%A3-gren-s-syndrome-in-brazilian-patients-infected-with-human-t-cell-lymphotropic-virus
#4
Daniela Assis do Vale, Jorge Casseb, Augusto César Penalva de Oliveira, Ivo Bussoloti Filho, Suzana Cantanhede Orsini Machado de Sousa, Karem López Ortega
BACKGROUND: Human T-lymphotropic virus type I (HTLV-I) is known to be associated with neoplastic and neurodegenerative changes, and it is believed to be associated with various systemic inflammatory diseases, including Sjögren's syndrome (SS). Although HTLV-I infection is endemic in Brazil, there is no information regarding the association between HTLV-I infection and SS in the Brazilian population. The objective of this study was to determine the prevalence of SS in HTLV-I-infected individuals and the prevalence of HTLV-I-infection in individuals diagnosed with SS...
December 7, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27925282/hypobaric-hypoxia-regulates-brain-iron-homeostasis-in-rats
#5
Yaru Li, Peng Yu, Shi-Yang Chang, Qiong Wu, Panpan Yu, Congcong Xie, Wenyue Wu, Baolu Zhao, Guofen Gao, Yan-Zhong Chang
Disruption of iron homeostasis in brain has been found to be closely involved in several neurodegenerative diseases. Recent studies have reported that appropriate intermittent hypobaric hypoxia played a protective role in brain injury caused by acute hypoxia. However, the mechanisms of this protective effect have not been fully understood. In this study, Sprague-Dawley rat models were developed by hypobaric hypoxia treatment in an altitude chamber, and the iron level and iron related protein levels were determined in rat brain after four weeks of treatment...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27924954/eeg-functional-network-topology-is-associated-with-disability-in-patients-with-amyotrophic-lateral-sclerosis
#6
Matteo Fraschini, Matteo Demuru, Arjan Hillebrand, Lorenza Cuccu, Silvia Porcu, Francesca Di Stefano, Monica Puligheddu, Gianluca Floris, Giuseppe Borghero, Francesco Marrosu
Amyotrophic Lateral Sclerosis (ALS) is one of the most severe neurodegenerative diseases, which is known to affect upper and lower motor neurons. In contrast to the classical tenet that ALS represents the outcome of extensive and progressive impairment of a fixed set of motor connections, recent neuroimaging findings suggest that the disease spreads along vast non-motor connections. Here, we hypothesised that functional network topology is perturbed in ALS, and that this reorganization is associated with disability...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924726/neurodegenerative-disease-a-perspective-on-cell-based-therapy-in-the-new-era-of-cell-free-nano-therapy
#7
Su M Metcalfe, Sean Bickerton, Tarek Fahmy
Neurodegenerative diseases (NDD) result in irreversible loss of neurons. Dementia develops when disease-induced neuronal loss becomes sufficient to impair both memory and cognitive functioning and, globally, dementia is increasing to epidemic proportions as populations age. In the current era of regenerative medicine intense activity is asking, can loss of endogenous neurons be compensated by replacement with exogenously derived cells that have either direct, or indirect, neurogenic capacity? But, more recently, excitement is growing around an emerging alternative to the cell-based approach - here nanotechnology for targeted delivery of growth factor aims to support and expand resident central nervous system (CNS) stem cells for endogenous repair...
December 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27924567/the-nuclear-translocation-of-erk
#8
Denise A Berti, Rony Seger
The ERK1 and ERK2 (ERK1/2) cascade is a central signaling pathway activated by a wide variety of extracellular agents that transmit the messages of G Protein Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs). Being such a central pathway, the activity of the cascade is well regulated, including by dynamic changes of the subcellular localization of components of the ERK1/2 cascade. In resting cells, ERK1/2 are localized in the cytosol due to their interactions with different anchoring proteins. After stimulation, ERK1/2 are phosphorylated by MEK1/2 on their regulatory TEY motif, which permits their detachment from the anchoring proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924561/detection-and-functional-analysis-of-sumo-modified-mek
#9
Yuji Kubota, Mutsuhiro Takekawa
Small ubiquitin-like modifier (SUMO) is a posttranslational protein modifier that binds target proteins covalently (protein sumoylation) and remarkably alters their functions. Protein sumoylation has been linked to various cellular functions such as cell division, DNA repair, and import of nuclear proteins. Thus, its dysregulation is implicated in diverse human diseases such as neurodegenerative disorders and cancers. We recently found that the kinase activity of MEK proteins, which function as central components of the ERK-MAPK cascade and amplify an extracellular proliferation signal, is negatively regulated by sumoylation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924559/isolation-and-characterization-of-intrinsically-active-mek-independent-mutants-of-mpk1-erk
#10
Tal Goshen-Lago, Dganit Melamed, Arie Admon, David Engelberg
The extracellular-regulated kinase (Erk) pathway is a major determinant in the control of diverse cellular processes, such as proliferation, differentiation, survival, and motility. The pathway executes its effects through kinases of the Erk family. Erks are not only critical for a variety of physiological processes, but are also associated with neurodegenerative diseases, cardiovascular diseases, diabetes and a large number of human cancers. However, the exact role of each Erk molecule in these biological and pathological processes is not fully determined...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924204/combined-use-of-a-double-lumen-tube-and-fogarty-catheter-to-prevent-the-endobronchial-spread-of-infection-a-case-report
#11
Jaewon Kim, Hyelim Lee, Han Park, Chang-Young Jeong
Huntington's disease is a neurodegenerative disorder with an autosomal dominant inheritance pattern. Patients with Huntington's disease show an increased risk of aspiration pneumonia when the pharyngeal muscle is invaded. We report a case of advanced-stage Huntington's disease in which the patient received right middle lobectomy for a lung abscess caused by repeated aspiration. The best lung isolation technique has not yet been established in these patients. We successfully performed selective lobar isolation of the right lower and middle lobes using a double lumen tube and a Fogarty embolectomy catheter...
December 2016: Korean Journal of Anesthesiology
https://www.readbyqxmd.com/read/27924190/network-analysis-of-human-post-mortem-microarrays-reveals-novel-genes-micrornas-and-mechanistic-scenarios-of-potential-importance-in-fighting-huntington-s-disease
#12
Sreedevi Chandrasekaran, Danail Bonchev
Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27923875/accounting-for-protein-subcellular-localization-a-compartmental-map-of-the-rat-liver-proteome
#13
Michel Jadot, Marielle Boonen, Jacqueline Thirion, Nan Wang, Jinchuan Xing, Caifeng Zhao, Abla Tannous, Meiqian Qian, Haiyan Zheng, John K Everett, Dirk F Moore, David E Sleat, Peter Lobel
Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle while a significant fraction may reside elsewhere...
December 6, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27923786/retinal-microvascular-network-alterations-potential-biomarkers-of-cerebrovascular-and-neural-diseases
#14
Delia Cabrera DeBuc, Gabor Mark Somfai, Akos Koller
Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric and developmental diseases. Thus, non-invasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because of the microvascular network of the retina and brain share in many aspects standard features in development, morphology, function and pathophysiology...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27923640/the-accumulation-of-brain-injury-leads-to-severe-neuropathological-and-neurobehavioral-changes-after-repetitive-mild-traumatic-brain-injury
#15
Huabin Gao, Zhaoli Han, Ruojing Bai, Shan Huang, Xintong Ge, Fanglian Chen, Ping Lei
Traumatic brain injury (TBI) is a major public health problem with long-term neurobehavioral sequela. The evidences have revealed that TBI is a risk factor for later development of neurodegenerative disease and both the single and repetitive brain injury can lead to the neurodegeneration. But whether the effects of accumulation play an important role in the neurodegenerative disease is still unknown. We utilized the Sprague Dawley (SD) rats to develop the animal models of repetitive mild TBI and single mild TBI in order to detect the neurobehavioral changes...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923633/diversity-of-glycosphingolipid-gm2-and-cholesterol-accumulation-in-npc1-patient-specific-ipsc-derived-neurons
#16
Michaela Trilck, Franziska Peter, Chaonan Zheng, Marcus Frank, Kostantin Dobrenis, Hermann Mascher, Arndt Rolfs, Moritz J Frech
Niemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. On the cellular level NPC1 mutations lead to an accumulation of cholesterol and gangliosides. As a thorough analysis of the severely affected neuronal cells is unfeasible in NPC1 patients, we recently described the cellular phenotype of neuronal cells derived from NPC1 patient iPSCs carrying the compound heterozygous mutation c.1836A>C/c.1628delC. Here we expanded the analysis to cell lines carrying the prevalent mutation c...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#17
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27923020/sex-on-the-brain-unraveling-the-differences-between-women-and-men-in-neurodegenerative-disease
#18
Mike May
No abstract text is available yet for this article.
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27922102/slc2a8-glut8-is-a-mammalian-trehalose-transporter-required-for-trehalose-induced-autophagy
#19
Allyson L Mayer, Cassandra B Higgins, Monique R Heitmeier, Thomas E Kraft, Xia Qian, Jan R Crowley, Krzysztof L Hyrc, Wandy L Beatty, Kevin E Yarasheski, Paul W Hruz, Brian J DeBosch
Trehalose is a disaccharide demonstrated to mitigate disease burden in multiple murine neurodegenerative models. We recently revealed that trehalose rapidly induces hepatic autophagy and abrogates hepatic steatosis by inhibiting hexose transport via the SLC2A family of facilitative transporters. Prior studies, however, postulate that intracellular trehalose is sufficient to induce cellular autophagy. The objective of the current study was to identify the means by which trehalose accesses the hepatocyte cytoplasm, and define the distal signaling mechanisms by which trehalose induces autophagy...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921253/aberrant-alterations-of-mitochondrial-factors-drp1-and-opa1-in-the-brains-of-scrapie-experiment-rodents
#20
Xiao -Dong Yang, Qi Shi, Jing Sun, Yan Lv, Yue Ma, Cao Chen, Kang Xiao, Wei Zhou, Xiao-Ping Dong
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed...
December 6, 2016: Journal of Molecular Neuroscience: MN
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