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https://www.readbyqxmd.com/read/28731438/evidence-that-the-human-innate-immune-peptide-ll-37-may-be-a-binding-partner-of%C3%A2-amyloid-%C3%AE-and-inhibitor-of%C3%A2-fibril-assembly
#1
Ersilia De Lorenzi, Marcella Chiari, Raffaella Colombo, Marina Cretich, Laura Sola, Renzo Vanna, Paola Gagni, Federica Bisceglia, Carlo Morasso, Jennifer S Lin, Moonhee Lee, Patrick L McGeer, Annelise E Barron
BACKGROUND: Identifying physiologically relevant binding partners of amyloid-β (Aβ) that modulate in vivo fibril formation may yield new insights into Alzheimer's disease (AD) etiology. Human cathelicidin peptide, LL-37, is an innate immune effector and modulator, ubiquitous in human tissues and expressed in myriad cell types. OBJECTIVE: We present in vitro experimental evidence and discuss findings supporting a novel hypothesis that LL-37 binds to Aβ42 and can modulate Aβ fibril formation...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730968/modulation-of-the-immune-system-for-the-treatment-of-glaucoma
#2
Katharina Bell, Nadine von Thun Und Hohenstein-Blaul, Julia Teister, Franz H Grus
At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730967/microglia-and-astrocytes-in-alzheimer-s-disease-implications-for-therapy
#3
Marc Fakhoury
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptide and the formation of neurofibrillary tangles (NFTs) in the brain. Over the past few years, mounting evidence has implicated sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730076/scutellaria-barbata-attenuates-diabetic-retinopathy-by-preventing-retinal-inflammation-and-the-decreased-expression-of-tight-junction-protein
#4
Xi-Yu Mei, Ling-Yu Zhou, Tian-Yu Zhang, Bin Lu, Li-Li Ji
AIM: To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28730074/protection-of-retinal-ganglion-cells-against-optic-nerve-injury-by-induction-of-ischemic-preconditioning
#5
Xia Liu, Jiu-Ping Liang, Ou Sha, Song-Juan Wang, Heng-Guo Li, Eric Y P Cho
AIM: To explore if ischemic preconditioning (IPC) can enhance the survival of retinal ganglion cells (RGCs) after optic nerve axotomy. METHODS: Twenty-four hours prior to retinal ischemia 60min or axotomy, IPC was applied for ten minutes in groups of (n=72) animals. The survival of RGCs, the cellular expression of heat shock protein 27 (HSP27) and heat shock protein 70 (HSP70) and the numbers of retinal microglia in the different groups were quantified at 7 and 14d post-injury...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729832/the-role-of-microglia-in-retinal-neurodegeneration-alzheimer-s-disease-parkinson-and-glaucoma
#6
REVIEW
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28729628/a-new-approach-for-ratiometric-in-vivo-calcium-imaging-of-microglia
#7
Bianca Brawek, Yajie Liang, Daria Savitska, Kaizhen Li, Natalie Fomin-Thunemann, Yury Kovalchuk, Elizabeta Zirdum, Johan Jakobsson, Olga Garaschuk
Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca(2+)-dependent, but our knowledge about in vivo Ca(2+) signalling in microglia is rudimentary. This is mostly due to technical reasons, as microglia largely resisted all attempts of in vivo labelling with Ca(2+) indicators...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729191/hypothermia-pretreatment-improves-cognitive-impairment-via-enhancing-synaptic-plasticity-in-a-traumatic-brain-injury-model
#8
Bingjin Liu, Lin Wang, Yun Cao, Weiqi Xu, Fangxiao Shi, Qing Tian, Xinwen Zhou
PosttraumatichypothermiaattenuatescognitivedeficitscausedbyTBIwhen it is administered at an early stage. However, little is known regarding the effect of hypothermia pretreatment on cognitive deficits one month after TBI. In the current study, the behavior test revealed that hypothermia pretreatment mitigates the learning and memory impairment induced by TBI in mice. Hypothermia treatment significantly increased the expression of PSD93, PSD95 and NR2B one month after TBI in the cortex and hippocampus compared with the normothermia group...
July 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28729074/proteomic-analysis-of-the-effects-of-nur77-on-lipopolysaccharide-induced-microglial-activation
#9
Yan Chen, Yuexinzi Jin, Hui Zhan, Jian Chen, Yanting Chen, Hailan Meng, Jiali Jin, Linjie Yu, Xiang Cao, Yun Xu
Microglia are critical components of the immune response in the central nervous system. Our study aims to explore potential role of Nur77 in lipopolysaccharide (LPS)-induced microglial activation. Primary wild-type and Nur77(-/-) microglia were stimulated with LPS and protein extracts were detected via mass spectrometry. Q-PCR and western blotting were performed to validate candidate proteins. A total of 2004 proteins were identified, with 749 and 677 significantly differentially expressed proteins in wild-type and Nur77(-/-) microglia in resting and activated states, respectively...
July 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28728016/location-location-location-microglia-are-where-they-live
#10
Margaret M McCarthy
A deep dive into microglia form and function reveals startling regional heterogeneity in number, morphology, activity, and transcriptomics in nuclei relevant to motor control and motivation (De Biase et al., 2017). Differences appear 2 weeks after birth, and depletion and recolonization in adulthood recapitulate the original phenotype, implicating local environment as mediators of microglial phenotype.
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28727115/the-microbiota-gut-brain-axis-as-a-key-regulator-of-neural-function-and-the-stress-response-implications-for-human-and-animal-health
#11
N C Wiley, T G Dinan, R P Ross, C Stanton, G Clarke, J F Cryan
The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#12
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28724755/trim33-tif1-%C3%AE-is-essential-for-macrophage-and-neutrophil-mobilisation-to-developmental-or-inflammatory-cues
#13
Doris Lou Demy, Muriel Tauzin, Mylène Lancino, Véronique le Cabec, Michael Redd, Emi Murayama, Isabelle Maridonneau-Parini, Nikolaus Trede, Philippe Herbomel
Macrophages infiltrate and establish in developing organs from an early stage, often before these have become vascularised. Similarly, leukocytes in general can quickly migrate through tissues to any site of wounding. This unique capacity is rooted in their characteristic amoeboid motility, the genetic basis of which is poorly known. Trim33 (Tif1-γ), a nuclear protein that associates with specific DNA binding transcription factors to modulate gene expression, has been found mainly involved in hematopoiesis and gene regulation by TGF-ß...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28723550/induced-pluripotent-stem-cell-derived-primitive-macrophages-provide-a-platform-for-modeling-tissue-resident-macrophage-differentiation-and-function
#14
Kazuyuki Takata, Tatsuya Kozaki, Christopher Zhe Wei Lee, Morgane Sonia Thion, Masayuki Otsuka, Shawn Lim, Kagistia Hana Utami, Kerem Fidan, Dong Shin Park, Benoit Malleret, Svetoslav Chakarov, Peter See, Donovan Low, Gillian Low, Marta Garcia-Miralles, Ruizhu Zeng, Jinqiu Zhang, Chi Ching Goh, Ahmet Gul, Sandra Hubert, Bernett Lee, Jinmiao Chen, Ivy Low, Nurhidaya Binte Shadan, Josephine Lum, Tay Seok Wei, Esther Mok, Shohei Kawanishi, Yoshihisa Kitamura, Anis Larbi, Michael Poidinger, Laurent Renia, Lai Guan Ng, Yochai Wolf, Steffen Jung, Tamer Önder, Evan Newell, Tara Huber, Eishi Ashihara, Sonia Garel, Mahmoud A Pouladi, Florent Ginhoux
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722716/alzheimer-s-disease-microglia
#15
Ioana Visan
No abstract text is available yet for this article.
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#16
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722234/minocycline-reduces-microgliosis-and-improves-subcortical-white-matter-function-in-a-model-of-cerebral-vascular-disease
#17
Yasmina Manso, Philip R Holland, Akihiro Kitamura, Stefan Szymkowiak, Jessica Duncombe, Edel Hennessy, James L Searcy, Martina Marangoni, Andrew D Randall, Jon T Brown, Barry W McColl, Karen Horsburgh
Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28721047/the-role-of-microglia-in-multiple-sclerosis
#18
REVIEW
Chun Luo, Chongdong Jian, Yuhan Liao, Qi Huang, Yuejuan Wu, Xixia Liu, Donghua Zou, Yuan Wu
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Microglia are the resident innate immune cells in the CNS; they play an important role in the processes of demyelination and remyelination in MS. Microglia can function as antigen-presenting cells and phagocytes. In the past, microglia were considered to be the same cell type as macrophages, and researchers have different opinions about the role of microglia in MS. This review focuses on the original classification of microglia and their role in the pathogenesis of MS...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28720882/cell-type-specific-differences-in-promoter-activity-of-the-als-linked-c9orf72-mouse-ortholog
#19
Abraham J Langseth, Juhyun Kim, Janet E Ugolino, Yajas Shah, Ho-Yon Hwang, Jiou Wang, Dwight E Bergles, Solange P Brown
A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of inherited forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Both loss-of-function and gain-of-function mechanisms have been proposed to underlie this disease, but the pathogenic pathways are not fully understood. To better understand the involvement of different cell types in the pathogenesis of ALS, we systematically analyzed the distribution of promoter activity of the mouse ortholog of C9orf72 in the central nervous system...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720702/identification-of-a-vesicular-atp-release-inhibitor-for-the-treatment-of-neuropathic-and-inflammatory-pain
#20
Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji
Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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