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Microglia apoE

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https://www.readbyqxmd.com/read/27885823/novel-functionalization-strategies-of-polymeric-nanoparticles-as-carriers-for-brain-medications
#1
Corinne Portioli, Michele Bovi, Donatella Benati, Marta Donini, Massimiliano Perduca, Alessandro Romeo, Stefano Dusi, Hugo L Monaco, Marina Bentivoglio
For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain barrier (BBB). Novel functionalization strategies, based on low-density lipoprotein receptor (LDLR) binding domain, have been here tested to increase the brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs, biodegradable and suited for biomedical applications. Custom-made PLGA NPs were functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS), highly expressed in the brain...
November 5, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27714634/zinc-oxide-nanoparticle-induces-microglial-death-by-nadph-oxidase-independent-reactive-oxygen-species-as-well-as-energy-depletion
#2
Anuj Kumar Sharma, Vikas Singh, Ruchi Gera, Mahaveer Prasad Purohit, Debabrata Ghosh
Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27708245/chronic-low-dose-rate-ionising-radiation-affects-the-hippocampal-phosphoproteome-in-the-apoe-alzheimer-s-mouse-model
#3
Stefan J Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka Iii, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin R Larsen, Soile Tapio
Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer´s model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27700119/biomimetic-apoe-reconstituted-high-density-lipoprotein-nanocarrier-for-blood-brain-barrier-penetration-and-amyloid-beta-targeting-drug-delivery
#4
Qingxiang Song, Huahua Song, Jianrong Xu, Jialin Huang, Meng Hu, Xiao Gu, Juan Chen, Gang Zheng, Hongzhuan Chen, Xiaoling Gao
Amyloid beta (Aβ) and its aggregation forms in the brain have been suggested as key targets for the therapy of Alzheimer's disease (AD). Therefore, the development of nanocarriers which possess both blood-brain barrier permeability and Aβ-targeting ability is of great importance for the intervention of AD. Here we constructed a biomimetic nanocarrier named apolipoprotein E (ApoE)-reconstituted high density lipoprotein nanocarrier (ANC) from recombinant ApoE and synthetic lipids to achieve the above goals...
October 4, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27477018/trem2-binds-to-apolipoproteins-including-apoe-and-clu-apoj-and-thereby-facilitates-uptake-of-amyloid-beta-by-microglia
#5
Felix L Yeh, Yuanyuan Wang, Irene Tom, Lino C Gonzalez, Morgan Sheng
Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD). Starting from an unbiased protein microarray screen, we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity...
July 20, 2016: Neuron
https://www.readbyqxmd.com/read/27425031/transcriptional-profiling-of-cd11c-positive-microglia-accumulating-around-amyloid-plaques-in-a-mouse-model-for-alzheimer-s-disease
#6
Willem Kamphuis, Lieneke Kooijman, Sjoerd Schetters, Marie Orre, Elly M Hol
Amyloid plaques in Alzheimer's disease (AD) mice are surrounded by activated microglia. The functional role of microglia activation in AD is not well understood; both detrimental and beneficial effects on AD progression have been reported. Here we show that the population of activated microglia in the cortex of the APPswe/PS1dE9 mouse AD model is divided into a CD11c-positive and a CD11c-negative subpopulation. Cd11c transcript levels and number of CD11c-positive microglia increase sharply when plaques start to occur and both parameters continue to rise in parallel with the age-related increasing plaque load...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27345627/probucol-inhibits-lps-induced-microglia-activation-and-ameliorates-brain-ischemic-injury-in-normal-and-hyperlipidemic-mice
#7
Yeon Suk Jung, Jung Hwa Park, Hyunha Kim, So Young Kim, Ji Young Hwang, Ki Whan Hong, Sun Sik Bae, Byung Tae Choi, Sae-Won Lee, Hwa Kyoung Shin
AIM: Increasing evidence suggests that probucol, a lipid-lowering agent with anti-oxidant activities, may be useful for the treatment of ischemic stroke with hyperlipidemia via reduction in cholesterol and neuroinflammation. In this study we examined whether probucol could protect against brain ischemic injury via anti-neuroinflammatory action in normal and hyperlipidemic mice. METHODS: Primary mouse microglia and murine BV2 microglia were exposed to lipopolysaccharide (LPS) for 3 h, and the release NO, PGE2, IL-1β and IL-6, as well as the changes in NF-κB, MAPK and AP-1 signaling pathways were assessed...
August 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27256292/microglial-immunophenotype-in-dementia-with-alzheimer-s-pathology
#8
Thais Minett, John Classey, Fiona E Matthews, Marie Fahrenhold, Mariko Taga, Carol Brayne, Paul G Ince, James A R Nicoll, Delphine Boche
BACKGROUND: Genetic risk factors for Alzheimer's disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes. METHODS: Using the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer's pathology...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27241720/an-apoe-derived-mimic-peptide-cog1410-alleviates-early-brain-injury-via-reducing-apoptosis-and-neuroinflammation-in-a-mouse-model-of-subarachnoid-hemorrhage
#9
Yue Wu, Jinwei Pang, Jianhua Peng, Fang Cao, Michael P Vitek, Fengqiao Li, Yong Jiang, Xiaochuan Sun
This study investigated the neuroprotective effects of COG1410, an apoliporotein E (apoE)-derived mimic peptide, against early brain injury (EBI) after subarachnoid hemorrhage (SAH). SAH was induced in C57BL/6J mice (n=68) by endovascular perforation. Mice received intravenous injection of COG1410 (2mg/kg) or equal volume of vehicle (saline). The mortality rate, neurological score, rotarod latencies, cell apoptosis, microglial activation, pro-inflammatory cytokines production and protein levels of apoptotic and inflammatory markers were assessed at 24h after sham operation or SAH...
August 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27235741/bexarotene-protects-against-traumatic-brain-injury-in-mice-partially-through-apolipoprotein-e
#10
Jianjun Zhong, Chongjie Cheng, Han Liu, Zhijian Huang, Yue Wu, Zhipeng Teng, Junchi He, Hongrong Zhang, Jinchuan Wu, Fang Cao, Li Jiang, Xiaochuan Sun
Bexarotene has been proved to have neuroprotective effects in many animal models of neurological diseases. However, its neuroprotection in traumatic brain injury (TBI) is still unknown. This study aims to explore the neuroprotective effects of bexarotene on TBI and its possible mechanism. Controlled cortical impact (CCI) model was used to simulate TBI in C57BL/6 mice as well as APOE gene knockout (APOE-KO) mice. After CCI, mice were daily dosed with bexarotene or vehicle solution intraperitoneally. The motor function, learning and memory, inflammatory factors, microglia amount, apoptosis condition around injury site and main side-effects were all measured...
May 25, 2016: Neuroscience
https://www.readbyqxmd.com/read/27100611/targeting-microglia-for-the-treatment-of-alzheimer-s-disease
#11
REVIEW
Paul D Wes, Faten A Sayed, Frédérique Bard, Li Gan
While histological changes in microglia have long been recognized as a pathological feature of Alzheimer's disease (AD), recent genetic association studies have also strongly implicated microglia in the etiology of the disease. Coding and noncoding polymorphisms in several genes expressed in microglia-including APOE, TREM2, CD33, GRN, and IL1RAP-alter AD risk, and therefore could be considered as entry points for therapeutic intervention. Furthermore, microglia may have a substantial effect on current amyloid β (Aβ) and tau immunotherapy approaches, since they are the primary cell type in the brain to mediate Fc receptor-facilitated antibody effector function...
October 2016: Glia
https://www.readbyqxmd.com/read/27057732/lxr-activation-protects-hippocampal-microvasculature-in-very-old-triple-transgenic-mouse-model-of-alzheimer-s-disease
#12
Adrián G Sandoval-Hernández, Alejandro Restrepo, Gloria P Cardona-Gómez, Gonzalo Arboleda
The vascular hypothesis of Alzheimer's disease postulates that disruption of the brain microvasculature is important for the accumulation of amyloid beta and increased neuroinflammation. Liver X Receptor agonist, GW3965, has been demonstrated to successfully modulate neuroinflammation and lipid metabolism in murine models of AD. This is partially due to increased expression of ApoE levels and increased mobility of endothelial progenitor cells. This paper analyzes changes in the neurovascular unit and in astrocytes and microglia markers following oral administration of GW3965 in a very old triple transgenic AD mice (3xTg-AD mice)...
May 16, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/26687817/plaque-associated-local-toxicity-increases-over-the-clinical-course-of-alzheimer-disease
#13
Alberto Serrano-Pozo, Rebecca A Betensky, Matthew P Frosch, Bradley T Hyman
Amyloid (senile) plaques, one of the two pathologic hallmarks of Alzheimer disease (AD), are associated with dystrophic neurites and glial responses, both astrocytic and microglial. Although plaque burden remains relatively stable through the clinical course of AD, whether these features of local plaque toxicity continue to worsen over the course of the disease is unclear. We performed an unbiased plaque-centered quantification of SMI312(+) dystrophic neurites, GFAP(+) reactive astrocytes, and IBA1(+) and CD68(+) activated microglia in randomly selected dense-core (Thioflavin-S(+)) plaques from the temporal neocortex of 40 AD subjects with a symptom duration ranging from 4 to 20 years, and nine nondemented control subjects with dense-core plaques...
February 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26674112/leukocyte-telomere-length-and-hippocampus-volume-a-meta-analysis
#14
Gustav Nilsonne, Sandra Tamm, Kristoffer N T Månsson, Torbjörn Åkerstedt, Mats Lekander
Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0...
2015: F1000Research
https://www.readbyqxmd.com/read/26512759/apoe-stabilization-by-exercise-prevents-aging-neurovascular-dysfunction-and-complement-induction
#15
Ileana Soto, Leah C Graham, Hannah J Richter, Stephen N Simeone, Jake E Radell, Weronika Grabowska, W Keith Funkhouser, Megan C Howell, Gareth R Howell
Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes...
October 2015: PLoS Biology
https://www.readbyqxmd.com/read/26374899/apolipoprotein-e-is-a-ligand-for-triggering-receptor-expressed-on-myeloid-cells-2-trem2
#16
Yuka Atagi, Chia-Chen Liu, Meghan M Painter, Xiao-Fen Chen, Christophe Verbeeck, Honghua Zheng, Xia Li, Rosa Rademakers, Silvia S Kang, Huaxi Xu, Steven Younkin, Pritam Das, John D Fryer, Guojun Bu
Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons...
October 23, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26268530/gwas-of-longitudinal-amyloid-accumulation-on-18f-florbetapir-pet-in-alzheimer-s-disease-implicates-microglial-activation-gene-il1rap
#17
Vijay K Ramanan, Shannon L Risacher, Kwangsik Nho, Sungeun Kim, Li Shen, Brenna C McDonald, Karmen K Yoder, Gary D Hutchins, John D West, Eileen F Tallman, Sujuan Gao, Tatiana M Foroud, Martin R Farlow, Philip L De Jager, David A Bennett, Paul S Aisen, Ronald C Petersen, Clifford R Jack, Arthur W Toga, Robert C Green, William J Jagust, Michael W Weiner, Andrew J Saykin
Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing...
October 2015: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/26254234/nadph-oxidase-2-derived-reactive-oxygen-species-in-the-hippocampus-might-contribute-to-microglial-activation-in-postoperative-cognitive-dysfunction-in-aged-mice
#18
Li-Li Qiu, Mu-Huo Ji, Hui Zhang, Jiao-Jiao Yang, Xiao-Ru Sun, Hui Tang, Jing Wang, Wen-Xue Liu, Jian-Jun Yang
Microglial activation plays a key role in the development of postoperative cognitive dysfunction (POCD). Nox2, one of the main isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the central nervous system, is a predominant source of reactive oxygen species (ROS) overproduction in phagocytes including microglia. We therefore hypothesized that Nox2-induced microglial activation is involved in the development of POCD. Sixteen-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery...
January 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/26185969/neuronal-regulation-of-neuroprotective-microglial-apolipoprotein-e-secretion-in-rat-in-vitro-models-of-brain-pathophysiology
#19
Elisabetta Polazzi, Ilaria Mengoni, Emiliano Peña-Altamira, Francesca Massenzio, Marco Virgili, Sabrina Petralla, Barbara Monti
Apolipoprotein E (ApoE) is mainly secreted by glial cells and is involved in many brain functions, including neuronal plasticity, β-amyloid clearance, and neuroprotection. Microglia--the main immune cells of the brain--are one source of ApoE, but little is known about the physiologic regulation of microglial ApoE secretion by neurons and whether this release changes under inflammatory or neurodegenerative conditions. Using rat primary neural cell cultures, we show that microglia release ApoE through a Golgi-mediated secretion pathway and that ApoE progressively accumulates in neuroprotective microglia-conditioned medium...
August 2015: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/26163517/combined-liver-x-receptor-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-treatment-reduces-amyloid-%C3%AE-levels-and-improves-behavior-in-amyloid-precursor-protein-presenilin-1-mice
#20
Rebecca Skerrett, Mateus P Pellegrino, Brad T Casali, Laura Taraboanta, Gary E Landreth
Alzheimer disease (AD) is characterized by the extracellular accumulation of amyloid β (Aβ), which is accompanied by a robust inflammatory response in the brain. Both of these pathogenic processes are regulated by nuclear receptors, including the liver X receptors (LXRs) and peroxisome-proliferator receptor γ (PPARγ). Agonists of LXRs have been demonstrated previously to reduce Aβ levels and improve cognitive deficits in AD mouse models by inducing the transcription and lipidation of apolipoprotein E (apoE)...
August 28, 2015: Journal of Biological Chemistry
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