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Microglia and lysosome

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https://www.readbyqxmd.com/read/28776681/another-piece-in-the-progranulin-puzzle-special-binding-between-progranulin-and-prosaposin-creates-additional-lysosomal-access-an-editorial-comment-for-the-interaction-between-progranulin-and-prosaposin-is-mediated-by-granulins-and-the-linker-region-between
#1
EDITORIAL
Philip Van Damme
Loss-of-function mutations in the gene encoding the growth factor progranulin cause degeneration of the ageing brain in a dose-dependent manner. While heterozygous mutations result in adult onset frontotemporal dementia, the much rarer homozygous null mutations cause an early onset lysosomal storage disorder. A better understanding of the biology of progranulin in the central nervous system is needed to find solutions for these incurable diseases. This Editorial highlights a study by Zhou et al. in the current issue of the Journal of Neurochemistry, in which the authors provide data that are a step towards this goal...
August 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28769785/amyloid-%C3%AE-induced-redistribution-of-transcriptional-factor-eb-and-lysosomal-dysfunction-in-primary-microglial-cells
#2
Xingzhi Guo, Peng Tang, Li Chen, Peng Liu, Chen Hou, Xin Zhang, Yue Liu, Li Chong, Xiaoqing Li, Rui Li
Impaired clearance of Amyloid β (Aβ) by microglia in the brain may be associated with the senile plaque formation, a pathological hallmark relevant to Alzheimer's disease. Microglial cells in the brain are not able to efficiently degrade Aβ, suggesting that microglial lysosome impairment may occur. However, the mechanism of Aβ-induced impairment of microglia remains poorly understood. We observed the effects of Aβ on the trafficking of nuclear transcriptional factor EB (TFEB), a master regulator of lysosome biogenesis, and the expression of a downstream osteoporosis-associated transmembrane protein 1 (OSTM1), a vital molecule involved in lysosome acidification in primary microglial cells...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28689984/local-cues-establish-and-maintain-region-specific-phenotypes-of-basal-ganglia-microglia
#3
Lindsay M De Biase, Kornel E Schuebel, Zachary H Fusfeld, Kamwing Jair, Isobel A Hawes, Raffaello Cimbro, Hai-Ying Zhang, Qing-Rong Liu, Hui Shen, Zheng-Xiong Xi, David Goldman, Antonello Bonci
Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28687233/overview-of-immune-abnormalities-in-lysosomal-storage-disorders
#4
REVIEW
Donato Rigante, Clelia Cipolla, Umberto Basile, Francesca Gulli, Maria Cristina Savastano
The critical relevance of the lysosomal compartment for normal cellular function can be proved by numbering the clinical phenotypes that arise in lysosomal storage disorders (LSDs), a group of around 70 different monogenic autosomal or X-linked syndromes, caused by specific lysosomal enzyme deficiencies: all LSDs are characterized by progressive accumulation of heterogeneous biologic materials in the lysosomes of various parts of the body such as viscera, skeleton, skin, heart, and central nervous system. At least a fraction of LSDs has been associated with mixed abnormalities involving the immune system, while some patients with LSDs may result more prone to autoimmune phenomena...
August 2017: Immunology Letters
https://www.readbyqxmd.com/read/28623605/cathepsin-c-aggravates-neuroinflammation-involved-in-disturbances-of-behaviour-and-neurochemistry-in-acute-and-chronic-stress-induced-murine-model-of-depression
#5
Yanli Zhang, Kai Fan, Yanna Liu, Gang Liu, Xiaohan Yang, Jianmei Ma
Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28623134/dysfunction-in-diurnal-synaptic-responses-and-social-behavior-abnormalities-in-cathepsin-s-deficient-mice
#6
Fumiko Takayama, Xinwen Zhang, Yoshinori Hayashi, Zhou Wu, Hiroshi Nakanishi
The expression of cathepsin S (CatS), a microglia-specific lysosomal cysteine protease in the brain, is regulated by the intrinsic microglial circadian clock. We herein report that the diurnal variation of evoked synaptic responses of cortical neurons disappeared in cathepsin S-deficient (CatS(-/-)) mice. The dendritic spine density of the cortical neurons was significantly reduced by incubation with a recombinant CatS. Furthermore, CatS(-/-) mice exhibited impaired social interaction and social novelty recognition in the three-chamber test...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28597061/progressive-accumulation-of-autofluorescent-granules-in-macrophages-in-rat-striatum-after-systemic-3-nitropropionic-acid-a-correlative-light-and-electron-microscopic-study
#7
Tae-Ryong Riew, Hong Lim Kim, Jeong-Heon Choi, Xuyan Jin, Yoo-Jin Shin, Mun-Yong Lee
A variety of tissue biomolecules and intracellular structures are known to be autofluorescent. However, autofluorescent signals in brain tissues often confound analysis of the fluorescent markers used for immunohistochemistry. While investigating tissue and cellular pathologies induced by 3-nitropropionic acid, a mitochondrial toxin selective for striatal neurons, we encountered many autofluorescent signals confined to the lesion core. These structures were excited by blue (wavelength = 488 nm) and yellow-orange (555 nm), but not by red (639 nm) or violet (405 nm) lasers, indicating that this autofluorescence overlaps with the emission spectra of commonly used fluorophores...
June 9, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28485547/pseudoginsenoside-f11-attenuates-cerebral-ischemic-injury-by%C3%A2-alleviating-autophagic-lysosomal-defects
#8
Yue-Yang Liu, Tian-Yu Zhang, Xue Xue, Dong-Mei Liu, Hao-Tian Zhang, Lin-Lin Yuan, Ying-Lu Liu, Han-Lin Yang, Shi-Bo Sun, Cheng Zhang, He-Song Xu, Chun-Fu Wu, Jing-Yu Yang
AIMS: Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke. METHODS: Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke...
July 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28479389/involvement-of-progranulin-in-modulating-neuroinflammatory-responses-but-not-neurogenesis-in-the-hippocampus-of-aged-mice
#9
Yanbo Ma, Takashi Matsuwaki, Keitaro Yamanouchi, Masugi Nishihara
It is well established that adult neurogenesis in the hippocampus declines with age. Our previous studies have suggested that progranulin (PGRN) has a facilitative effect on hippocampal neurogenesis. We have also shown that PGRN plays a role in suppressing excessive neuroinflammatory responses in the cortex and thalamus after brain injury and aging, respectively. However, the roles of PGRN in modulating neurogenesis and neuroinflammatory responses in the hippocampus of aged animals are not yet understood. In the present study, we investigated neurogenesis and neuroinflammation-related responses in the hippocampus of young (15-week-old) and old (135-week-old) wild-type and PGRN-deficient male mice...
September 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28476637/the-critical-role-of-nramp1-in-degrading-%C3%AE-synuclein-oligomers-in-microglia-under-iron-overload-condition
#10
Kuo-Chen Wu, Horng-Huei Liou, Yu-Han Kao, Chih-Yu Lee, Chun-Jung Lin
Oligomeric α-synuclein is a key mediator in the pathogenesis of Parkinson's disease (PD) and is mainly cleared by autophagy-lysosomal pathway, whose dysfunction results in the accumulation and cell-to-cell transmission of α-synuclein. In this study, concomitant with the accumulation of iron and oligomeric α-synuclein, higher expression of a lysosomal iron transporter, natural resistance-associated macrophage protein-1 (Nramp1), was observed in microglia in post-mortem striatum of sporadic PD patients. Using Nramp1-deficient macrophage (RAW264...
May 2, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28387679/orexin-impairs-the-phagocytosis-and-degradation-of-amyloid-%C3%AE-fibrils-by-microglial-cells
#11
Hoyoung An, Mi-Hyang Cho, Dong-Hou Kim, Seockhoon Chung, Seung-Yong Yoon
BACKGROUND: Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer's disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce. OBJECTIVE: To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28379303/restoring-neuronal-progranulin-reverses-deficits-in-a-mouse-model-of-frontotemporal-dementia
#12
Andrew E Arrant, Anthony J Filiano, Daniel E Unger, Allen H Young, Erik D Roberson
Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotional behaviour. GRN mutations are thought to cause frontotemporal dementia through progranulin haploinsufficiency, therefore, boosting progranulin expression from the intact allele is a rational treatment strategy. However, this approach has not been tested in an animal model of frontotemporal dementia and it is unclear if boosting progranulin could correct pre-existing deficits...
March 29, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#13
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28282924/autophagy-and-microglia-novel-partners-in-neurodegeneration-and-aging
#14
REVIEW
Ainhoa Plaza-Zabala, Virginia Sierra-Torre, Amanda Sierra
Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases...
March 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28181394/effects-of-silver-nanoparticles-on-the-interactions-of-neuron-and-glia-like-cells-toxicity-uptake-mechanisms-and-lysosomal-tracking
#15
I-Lun Hsiao, Yi-Kong Hsieh, Chun-Yu Chuang, Chu-Fang Wang, Yuh-Jeen Huang
Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono- and co-culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation...
June 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28160018/erratum-to-metformin-increases-phagocytosis-and-acidifies-lysosomal-endosomal-compartments-in-ampk-dependent-manner-in-rat-primary-microglia
#16
Krzysztof Łabuzek, Sebastian Liber, Bożena Gabryel, Jakub Adamczyk, Bogusław Okopień
No abstract text is available yet for this article.
March 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28159556/activated-microglia-trigger-inflammasome-activation-and-lysosomal-destabilization-in-human-rpe-cells
#17
Christopher Nebel, Alexander Aslanidis, Khalid Rashid, Thomas Langmann
Activation of the innate immune system plays a major role in retinal degenerative diseases including age-related macular degeneration (AMD). In this study, we investigated whether reactive microglia trigger and sustain NLRP3 inflammasome activation in human retinal pigment epithelium (ARPE-19) cells. Specifically, we analyzed the potential of cell culture supernatants from lipopolysaccharide (LPS)-stimulated human microglia in combination with the lysosomal destabilization agent Leu-Leu-O-Me (LLOMe) to activate the inflammasome in ARPE-19 cells...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27931227/epigenetics-of-amphetamine-induced-sensitization-hdac5-expression-and-microrna-in-neural-remodeling
#18
Philip K Liu, Christina H Liu
BACKGROUND: Histone deacetylase (HDAC) activities modify chromatin structure and play a role in learning and memory during developmental processes. Studies of adult mice suggest HDACs are involved in neural network remodeling in brain repair, but its function in drug addiction is less understood. We aimed to examine in vivo HDAC5 expression in a preclinical model of amphetamine-induced sensitization (AIS) of behavior. We generated specific contrast agents to measure HDAC5 levels by in vivo molecular contrast-enhanced (MCE) magnetic resonance imaging (MRI) in amphetamine-naïve mice as well as in mice with AIS...
December 8, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27889490/inhibition-of-cathepsin-x-reduces-the-strength-of-microglial-mediated-neuroinflammation
#19
Anja Pišlar, Biljana Božić, Nace Zidar, Janko Kos
Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important mediators of the inflammation involved in lipopolysaccharide (LPS)-induced neuroinflammation. The current study was undertaken to investigate the role of cathepsin X and its molecular target, γ-enolase, in neuroinflammation and to elucidate the underlying mechanism...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27888296/toll-like-receptor-2-is-increased-in-neurons-in-parkinson-s-disease-brain-and-may-contribute-to-alpha-synuclein-pathology
#20
Nicolas Dzamko, Amanda Gysbers, Gayathri Perera, Anita Bahar, Amrita Shankar, Jianqun Gao, YuHong Fu, Glenda M Halliday
Inflammation is likely a key contributor to the pathogenesis of Parkinson's disease (PD), a progressively debilitating neurodegenerative disease that is accompanied by a pathological accumulation of the α-synuclein protein in a staged manner through the brain. What leads to the accumulation of α-synuclein in PD and how this relates to inflammatory pathways, however, is not entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation and, in particular, TLR2 is increasingly being implicated in PD...
February 2017: Acta Neuropathologica
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