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https://www.readbyqxmd.com/read/28641287/chrysophanol-suppressed-glutamate-induced-hippocampal-neuronal-cell-death-via-regulation-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#1
Unbin Chae, Ju-Sik Min, Hyun Hee Leem, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28641113/enhanced-functional-genomic-screening-identifies-novel-mediators-of-dual-leucine-zipper-kinase-dependent-injury-signaling-in-neurons
#2
Derek S Welsbie, Katherine L Mitchell, Vinod Jaskula-Ranga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E Martin, Ping-Wu Zhang, Yan Ge, Yukan Duan, John Fuller, Byung-Jin Kim, Eman Hamed, Xitiz Chamling, Lei Lei, Iain D C Fraser, Ze'ev A Ronai, Cynthia A Berlinicke, Donald J Zack
Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641106/antisense-oligonucleotides-translation-from-mouse-models-to-human-neurodegenerative-diseases
#3
REVIEW
Kathleen M Schoch, Timothy M Miller
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640972/understanding-adaptogenic-activity-specificity-of-the-pharmacological-action-of-adaptogens-and-other-phytochemicals
#4
REVIEW
Alexander Panossian
Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-pre-requisites-for-neurodegenerative-disorders
#5
Joyce Ka Yu Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's Disease (AD) and Parkinson's Disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g. superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28640595/detection-and-characterization-of-small-molecule-interactions-with-fibrillar-protein-aggregates-using-microscale-thermophoresis
#6
Emily Fisher, Yanyan Zhao, Robert Richardson, Malgorzata Janik, Alexander K Buell, Franklin I Aigbirhio, Gergely Toth
Neurodegenerative diseases such as Parkinson's and Alzheimer's disease share the pathological hallmark of fibrillar protein aggregates. The specific detection of these protein aggregates by positron emission tomography (PET) in the patient brain can yield valuable information for diagnosis and disease progression. However, the identification of novel small compounds that bind fibrillar protein aggregates has been a challenge. In this study, microscale thermophoresis (MST) was applied to assess the binding affinity of known small molecule ligands of α-synuclein fibrils, which were also tested in parallel in a Thioflavin T fluorescence competition assay for further validation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28637276/repetitive-element-transcripts-are-elevated-in-the-brain-of-c9orf72-als-ftld-patients
#7
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/28636962/reactive-astrocytes-production-function-and-therapeutic-potential
#8
REVIEW
Shane A Liddelow, Ben A Barres
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636913/heterogeneous-tau-tubulin-complexes-accelerate-microtubule-polymerization
#9
Xiao-Han Li, Elizabeth Rhoades
Tau is an intrinsically disordered protein with a central role in the pathology of a number of neurodegenerative diseases. Tau normally functions to stabilize neuronal microtubules, although the mechanism underlying this function is not well understood. Of note is that the interaction between tau and soluble tubulin, which has implications both in understanding tau function as well as its role in disease, is underexplored. Here we investigate the relationship between heterogeneity in tau-tubulin complexes and tau function...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636787/a-co-drug-conjugate-of-naringenin-and-lipoic-acid-mediates-neuroprotection-in-a-rat-model-of-oxidative-stress
#10
Tarek M Saleh, Monique C Saleh, Barry J Connell, Yang-Heon Song
Using our in vitro and in vivo models of oxidative stress, the current study was designed to determine the neuroprotective potential of naringenin, alone or in combination with lipoic acid. In our mixed neuronal culture exposed to hypoxia and subsequent reoxygenation, naringenin was shown to provide significant neuroprotection against cell death at a concentration of 2.5 μM. Lipoic acid (LA) did not produce neuroprotection at any concentration tested (0.25 to 100 μM). In contrast, when naringenin was covalently combined with LA, producing a novel compound named "VANL-100", significant neuroprotection was observed at a concentration as low as 2 x 10(-2) μM (100-fold more potent)...
June 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28636179/discontinuation-and-non-publication-of-neurodegenerative-disease-trials-a-cross-sectional-analysis
#11
J D Stefaniak, T C H Lam, N E Sim, R Al-Shahi Salman, D P Breen
BACKGROUND AND PURPOSE: Trial discontinuation and non-publication represent major sources of research waste in clinical medicine. No previous studies have investigated non-dissemination bias in clinical trials of neurodegenerative diseases. METHODS: ClinicalTrials.gov was searched for all randomized, interventional, phase II-IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease...
June 21, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28636006/copper-ion-interaction-with-the-rnase-catalytic-site-fragment-of-the-angiogenin-protein-an-experimental-and-theoretical-investigation
#12
Antonio Magrì, Giovanni Tabbì, Raffaella Breglia, Luca De Gioia, Piercarlo Fantucci, Maurizio Bruschi, Raffaele P Bonomo, Diego La Mendola
The angiogenin protein (Ang) is a member of the vertebrate-specific secreted ribonucleases and one of the most potent angiogenic factors known. Ang is a normal constituent of human plasma and its concentration increases under some physiological and pathological conditions to promote neovascularization. Ang was originally identified as an angiogenic tumour factor, but its biological activity has been found to extend from inducing angiogenesis to promoting cell survival in different neurodegenerative diseases...
June 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#13
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635649/the-sea-urchin-arbacia-lixula-a-novel-natural-source-of-astaxanthin
#14
Paola Cirino, Christophe Brunet, Martina Ciaravolo, Christian Galasso, Luigi Musco, Tomás Vega Fernández, Clementina Sansone, Alfonso Toscano
Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ's), such as echinochrome A. Astaxanthin is known to have particular bioactivity for the prevention of neurodegenerative diseases. This carotenoid is produced by microalgae, while several marine invertebrates can bioaccumulate or synthetize it from metabolic precursors...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28635376/advances-in-understanding-the-role-of-disease-associated-proteins-in-spinal-muscular-atrophy
#15
Seyyedmohsen Hosseinibarkooie, Svenja Schneider, Brunhilde Wirth
Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by alpha motor neuron loss in the spinal cord due to reduced survival of motor neuron (SMN) protein level. While the genetic basis of SMA is well described, the specific molecular pathway underlying SMA is still not fully understood. Areas covered: This review discusses the recent advancements in understanding the molecular pathways in SMA using different omics approaches and genetic modifiers identified in both vertebrate and invertebrate systems...
June 21, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28635330/multiple-functions-of-insulin-degrading-enzyme-a-metabolic-crosslight
#16
Grazia R Tundo, Diego Sbardella, Chiara Ciaccio, Giuseppe Grasso, Magda Gioia, Andrea Coletta, Fabio Polticelli, Donato Di Pierro, Danilo Milardi, Peter Van Endert, Stefano Marini, Massimo Coletta
Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as β-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28634902/therapeutic-potential-of-baicalein-in-alzheimer-s-disease-and-parkinson-s-disease
#17
Yanwei Li, Jinying Zhao, Christian Hölscher
Alzheimer's disease and Parkinson's disease are the two most common, progressive central neurodegenerative diseases affecting the population over the age of 60 years. Apart from treatments that temporarily improve symptoms, there is no medicine currently available to inhibit or reverse the progression of Alzheimer's disease and Parkinson's disease. In traditional Chinese medicine, the root of Scutellaria baicalensis Georgi is a classic compatible component in the decoction of herbal medicine used for treating central nervous system diseases...
June 20, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28634681/microtubule-affinity-regulating-kinases-are-potential-druggable-targets-for-alzheimer-s-disease
#18
REVIEW
Narendran Annadurai, Khushboo Agrawal, Petr Džubák, Marián Hajdúch, Viswanath Das
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects normal functions of the brain. Currently, AD is one of the leading causes of death in developed countries and the only one of the top ten diseases without a means to prevent, cure, or significantly slow down its progression. Therefore, newer therapeutic concepts are urgently needed to improve survival and the quality of life of AD patients. Microtubule affinity-regulating kinases (MARKs) regulate tau-microtubule binding and play a crucial role in neurons...
June 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28634653/assessing-the-combined-toxicity-of-bmaa-and-its-isomers-2-4-dab-and-aeg-in-vitro-using-human-neuroblastoma-cells
#19
Brendan J Main, Kenneth J Rodgers
The non-protein amino acid (NPAA) ß-methylamino-L-alanine (BMAA) is produced by a diverse range of cyanobacteria, diatoms and dinoflagellates, and is present in both aquatic and terrestrial ecosystems globally. Exposure to BMAA has been implicated in the development of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). BMAA is often found in nature along with its structural isomers 2,4-diaminobutyric acid (2,4-DAB) and aminoethylglycine (AEG); however, the toxicity of these NPAAs in combination has not been examined...
June 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28634568/sirtuin-2-protects-neural-cells-from-oxidative-stress-and-is-elevated-in-neurodegeneration
#20
Preeti Singh, Peter S Hanson, Christopher M Morris
Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson's disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation...
2017: Parkinson's Disease
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