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https://www.readbyqxmd.com/read/29067327/zfra-restores-memory-deficits-in-alzheimer-s-disease-triple-transgenic-mice-by-blocking-aggregation-of-trappc6a%C3%AE-sh3glb2-tau-and-amyloid-%C3%AE-and-inflammatory-nf-%C3%AE%C2%BAb-activation
#1
Ming-Hui Lee, Yao-Hsiang Shih, Sing-Ru Lin, Jean-Yun Chang, Yu-Hao Lin, Chun-I Sze, Yu-Min Kuo, Nan-Shan Chang
INTRODUCTION: Zinc finger-like protein that regulates apoptosis (Zfra) is a naturally occurring 31-amino-acid protein. Synthetic peptides Zfra1-31 and Zfra4-10 are known to effectively block the growth of many types of cancer cells. METHODS: Ten-month-old triple-transgenic (3×Tg) mice for Alzheimer's disease (AD) received synthetic Zfra peptides via tail vein injections, followed by examining restoration of memory deficits. RESULTS: Zfra significantly downregulated TRAPPC6AΔ, SH3GLB2, tau, and amyloid β (Αβ) aggregates in the brains of 3×Tg mice and effectively restored their memory capabilities...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28856541/glycoprotein-nmb-an-emerging-role-in-neurodegenerative-disease
#2
REVIEW
Kevin M Budge, Matthew L Neal, Jason R Richardson, Fayez F Safadi
Neurodegeneration is characterized by severe neuronal loss leading to the cognitive and physical impairments that define various neurodegenerative diseases. Neuroinflammation is one hallmark of neurodegenerative diseases and can ultimately contribute to disease progression. Increased inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1 β), and tumor necrosis factor-α (TNF-α) are associated with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)...
August 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28442677/1-2-3-triazolyl-esterization-of-pak1-blocking-propolis-ingredients-artepillin-c-arc-and-caffeic-acid-ca-for-boosting-their-anti-cancer-anti-pak1-activities-along-with-cell-permeability
#3
Hideaki Takahashi, Binh Cao Quan Nguyen, Yoshihiro Uto, Md Shahinozzaman, Shinkichi Tawata, Hiroshi Maruta
Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1. However, mainly due to their COOH moiety, cell-permeability of these herbal compounds is rather limited. Thus, in this study, in an attempt to increase their cell-permeability without any significant loss of their water-solubility, we have esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through Click Chemistry. We found that this esterization boosts the anti-cancer activity of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent growth of A549 lung cells, but show no effect on the PAK1-independent growth of B16F10 melanoma cells...
May 30, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28368280/x-ray-crystal-structure-of-human-calcium-bound-s100a1
#4
Zephan Melville, Ehson Aligholizadeh, Laura E McKnight, Dylan J Weber, Edwin Pozharski, David J Weber
S100A1 is a member of the S100 family of Ca(2+)-binding proteins and regulates several cellular processes, including those involved in Ca(2+) signaling and cardiac and skeletal muscle function. In Alzheimer's disease, brain S100A1 is overexpressed and gives rise to disease pathologies, making it a potential therapeutic target. The 2.25 Å resolution crystal structure of Ca(2+)-S100A1 is solved here and is compared with the structures of other S100 proteins, most notably S100B, which is a highly homologous S100-family member that is implicated in the progression of malignant melanoma...
April 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28225789/non-melanoma-skin-cancer-and-risk-of-alzheimer-s-disease-and-all-cause-dementia
#5
Sigrun A J Schmidt, Anne G Ording, Erzsébet Horváth-Puhó, Henrik T Sørensen, Victor W Henderson
Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC), but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome) and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221) and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097)...
2017: PloS One
https://www.readbyqxmd.com/read/27942349/the-risks-and-benefits-of-sun-exposure-2016
#6
REVIEW
David G Hoel, Marianne Berwick, Frank R de Gruijl, Michael F Holick
Public health authorities in the United States are recommending that men, women and children reduce their exposure to sunlight, based on concerns that this exposure will promote skin cancer. On the other hand, data show that increasing numbers of Americans suffer from vitamin D deficiencies and serious health problems caused by insufficient sun exposure. The body of science concerning the benefits of moderate sun exposure is growing rapidly, and is causing a different perception of sun/UV as it relates to human health...
January 2016: Dermato-endocrinology
https://www.readbyqxmd.com/read/27831506/causes-of-death-among-cancer-patients
#7
N G Zaorsky, T M Churilla, B L Egleston, S G Fisher, J A Ridge, E M Horwitz, J E Meyer
Background: The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. Patients and methods: US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27687691/expression-of-b4galnt1-an-essential-glycosyltransferase-for-the-synthesis-of-complex-gangliosides-suppresses-bace1-degradation-and-modulates-app-processing
#8
Tokiaki Yamaguchi, Yoshio Yamauchi, Keiko Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Qing Zhang, Tetsuya Okajima, Koichi Furukawa
Alzheimer's disease (AD) is the most prevalent form of dementia characterized by the extracellular accumulation of amyloid β (Aβ) peptides, which are produced by proteolytic cleavages of amyloid precursor protein (APP). Gangliosides are involved in AD pathophysiology including Aβ deposition and APP processing, yet the detailed mechanisms are not fully understood. Here we examined how changes in the carbohydrate moiety of gangliosides alter APP processing in human melanoma cells, neuroectoderm-derived cells...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27397068/inflammasome-as-a-key-pathogenic-mechanism-in-endometriosis
#9
Pedro Bullon, Jose Manuel Navarro
BACKGROUND: Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. OBJECTIVES: Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome. METHOD: Literature review for the updating of data to give new clues for different options of treatments...
2017: Current Drug Targets
https://www.readbyqxmd.com/read/27382195/apolipoprotein-a-i-a-molecule-of-diverse-function
#10
REVIEW
Manaswini Mangaraj, Rachita Nanda, Suchismita Panda
Apolipoprotein A-I (apo A-I) an indispensable component and a major structural protein of high-density lipoprotein (HDL), plays a vital role in reverse cholesterol transport and cellular cholesterol homeostasis since its identification. Its multifunctional role in immunity, inflammation, apoptosis, viral, bacterial infection etc. has crossed its boundary of its potential of protecting cardiovascular system and lowering cardiovascular disease risk, attributing HDL to be known as a protective fat removal particle...
July 2016: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/27338620/dna-aptamers-raised-against-ages-as-a-blocker-of-various-aging-related-disorders
#11
Sho-Ichi Yamagishi, Kensei Taguchi, Kei Fukami
A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs)...
August 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/26391552/understanding-the-multifaceted-role-of-ectonucleotide-pyrophosphatase-phosphodiesterase-2-enpp2-and-its-altered-behaviour-in-human-diseases
#12
REVIEW
R P Cholia, H Nayyar, R Kumar, A K Mantha
Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) also known as Autotaxin, is a secreted lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) into Lysophosphatidic acid (LPA). LPA is the bioactive product of ENPP2 enzyme, which induces diverse signalling pathways via six LPA-G-protein coupled receptors (GPCRs). ENPP2 is an essential protein for normal development and its altered expression is associated with various human diseases. Cellular ENPP2 silencing results in lethality at the embryonic stage in mice...
2015: Current Molecular Medicine
https://www.readbyqxmd.com/read/25961655/masitinib-for-the-treatment-of-mild-to-moderate-alzheimer-s-disease
#13
REVIEW
Jaume Folch, Dmitry Petrov, Miren Ettcheto, Ignacio Pedrós, Sonia Abad, Carlos Beas-Zarate, Alberto Lazarowski, Miguel Marin, Jordi Olloquequi, Carme Auladell, Antoni Camins
Alzheimer's disease (AD) is a degenerative neurological disorder that is the most common cause of dementia and disability in older patients. Available treatments are symptomatic in nature and are only sufficient to improve the quality of life of AD patients temporarily. A potential strategy, currently under investigation, is to target cell-signaling pathways associated with neurodegeneration, in order to decrease neuroinflammation, excitotoxicity, and to improve cognitive functions. Current review centers on the role of neuroinflammation and the specific contribution of mast cells to AD pathophysiology...
June 2015: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/25744023/neuronal-nlrp1-inflammasome-activation-of-caspase-1-coordinately-regulates-inflammatory-interleukin-1-beta-production-and-axonal-degeneration-associated-caspase-6-activation
#14
V Kaushal, R Dye, P Pakavathkumar, B Foveau, J Flores, B Hyman, B Ghetti, B H Koller, A C LeBlanc
Neuronal active Caspase-6 (Casp6) is associated with Alzheimer disease (AD), cognitive impairment, and axonal degeneration. Caspase-1 (Casp1) can activate Casp6 but the expression and functionality of Casp1-activating inflammasomes has not been well-defined in human neurons. Here, we show that primary cultures of human CNS neurons expressed functional Nod-like receptor protein 1 (NLRP1), absent in melanoma 2, and ICE protease activating factor, but not the NLRP3, inflammasome receptor components. NLRP1 neutralizing antibodies in a cell-free system, and NLRP1 siRNAs in neurons hampered stress-induced Casp1 activation...
October 2015: Cell Death and Differentiation
https://www.readbyqxmd.com/read/25560640/phenome-genome-association-studies-of-pancreatic-cancer-new-targets-for-therapy-and-diagnosis
#15
Ramaswamy Narayanan
BACKGROUND: Pancreatic cancer, has a very high mortality rate and requires novel molecular targets for diagnosis and therapy. Genetic association studies over databases offer an attractive starting point for gene discovery. MATERIALS AND METHODS: The National Center for Biotechnology Information (NCBI) Phenome Genome Integrator (PheGenI) tool was enriched for pancreatic cancer-associated traits. The genes associated with the trait were characterized using diverse bioinformatics tools for Genome-Wide Association (GWA), transcriptome and proteome profile and protein classes for motif and domain...
January 2015: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/25400589/association-of-cancer-history-with-alzheimer-s-disease-onset-and-structural-brain-changes
#16
Kelly N H Nudelman, Shannon L Risacher, John D West, Brenna C McDonald, Sujuan Gao, Andrew J Saykin
Epidemiological studies show a reciprocal inverse association between cancer and Alzheimer's disease (AD). The common mechanistic theory for this effect posits that cells have an innate tendency toward apoptotic or survival pathways, translating to increased risk for either neurodegeneration or cancer. However, it has been shown that cancer patients experience cognitive dysfunction pre- and post-treatment as well as alterations in cerebral gray matter density (GMD) on MRI. To further investigate these issues, we analyzed the association between cancer history (CA±) and age of AD onset, and the relationship between GMD and CA± status across diagnostic groups in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort study...
2014: Frontiers in Physiology
https://www.readbyqxmd.com/read/25207059/the-multiple-life-of-nerve-growth-factor-tribute-to-rita-levi-montalcini-1909-2012
#17
REVIEW
Luigi Aloe, George N Chaldakov
At the end of the 19(th) century, it was envisaged by Santiago Ramon y Cajal, but not, proven, that life at the neuronal level requires trophic support. The proof was obtained in the early 1950's by work initiated by Rita Levi-Montalcini (RLM) discovering the nerve growth factor (NGF). Today, NGF and its relatives, collectively designated neurotrophins, are well recognized as mediators of multiple biological phenomena in health and disease, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects...
March 2013: Balkan Medical Journal
https://www.readbyqxmd.com/read/25061726/cudarflavone-b-provides-neuroprotection-against-glutamate-induced-mouse-hippocampal-ht22-cell-damage-through-the-nrf2-and-pi3k-akt-signaling-pathways
#18
Dong-Sung Lee, Wonmin Ko, Dong-Cheol Kim, Youn-Chul Kim, Gil-Saeng Jeong
Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Alzheimer's disease, Parkinson's disease, and ischemia. Nrf2 signaling-mediated heme oxygenase (HO)-1 expression acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases. Cudraflavone B is a prenylated flavone isolated from C. tricuspidata which has shown anti-proliferative activity, mouse brain monoamine oxidase (MAO) inhibitory effects, apoptotic actions in human gastric carcinoma cells and mouse melanoma cells, and hepatoprotective activity...
July 24, 2014: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/25058637/is-the-risk-of-motor-neuron-disease-increased-or-decreased-after-cancer-an-australian-case-control-study
#19
Alex Stoyanov, Roger Pamphlett
Cancer appears to be inversely associated with both Alzheimer's and Parkinson's disease. The relationship between cancer and sporadic motor neuron disease (SMND), however, remains uncertain. Most previous cancer-SMND studies have been undertaken in northern hemisphere populations. We therefore undertook a case-control study to see if a link between cancer and SMND exists in an Australian population. A questionnaire was used to compare past cancer diagnoses in 739 SMND patients and 622 controls, recruited across Australia...
2014: PloS One
https://www.readbyqxmd.com/read/24929653/modelling-human-protein-interaction-networks-as-metric-spaces-has-potential-in-disease-research-and-drug-target-discovery
#20
Emad Fadhal, Eric C Mwambene, Junaid Gamieldien
BACKGROUND: We have recently shown by formally modelling human protein interaction networks (PINs) as metric spaces and classified proteins into zones based on their distance from the topological centre that hub proteins are primarily centrally located. We also showed that zones closest to the network centre are enriched for critically important proteins and are also functionally very specialised for specific 'house keeping' functions. We proposed that proteins closest to the network centre may present good therapeutic targets...
2014: BMC Systems Biology
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