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https://www.readbyqxmd.com/read/29183796/heat-shock-protein-70-suppresses-neuroinflammation-induced-by-%C3%AE-synuclein-in-astrocytes
#1
Wen-Wen Yu, Sheng-Nan Cao, Cai-Xia Zang, Lu Wang, Han-Yu Yang, Xiu-Qi Bao, Dan Zhang
Neuroinflammation triggered by activation of glial cells plays an important role in the pathophysiology of several neurodegenerative diseases including Parkinson's disease (PD). Besides microglia, astrocytes are also critical in initiating and perpetuating inflammatory process associated with PD. Heat shock protein 70 (Hsp70) is originally described as intracellular chaperone, however, recent study revealed that it had anti-inflammatory effects as well. The present study is designed to investigate whether Hsp70 mediates neuroinflammation in astrocytes...
November 25, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29181664/immunomorphological-changes-in-the-olfactory-bulbs-of-rats-after-intranasal-administration-of-rotenone
#2
D N Voronkov, K A Kutukova, M V Ivanov, R M Khudoerkov
Changes in the structure of the olfactory bulbs after long-term intranasal administration of pesticide rotenone, a classical inductor of parkinsonism, to rats were studied by the methods of immunomorphology. In rats intranasally receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a decrease in the density of dopaminergic neurons and the area of astrocyte processes in the olfactory bulbs, activation of microglia in the glomerular layer, and enhanced α-synuclein phosphorylation and its accumulation in the bodies of mitral layer neurons were observed...
November 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29162163/%C3%AE-synuclein-fibrils-recruit-peripheral-immune-cells-in-the-rat-brain-prior-to-neurodegeneration
#3
Ashley S Harms, Vedad Delic, Aaron D Thome, Nicole Bryant, Zhiyong Liu, Sidhanth Chandra, Asta Jurkuvenaite, Andrew B West
Genetic variation in a major histocompatibility complex II (MHCII)-encoding gene (HLA-DR) increases risk for Parkinson disease (PD), and the accumulation of MHCII-expressing immune cells in the brain correlates with α-synuclein inclusions. However, the timing of MHCII-cell recruitment with respect to ongoing neurodegeneration, and the types of cells that express MHCII in the PD brain, has been difficult to understand. Recent studies show that the injection of short α-synuclein fibrils into the rat substantia nigra pars compacta (SNpc) induces progressive inclusion formation in SNpc neurons that eventually spread to spiny projection neurons in the striatum...
November 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29155051/peripheral-monocyte-entry-is-required-for-alpha-synuclein-induced-inflammation-and-neurodegeneration-in-a-model-of-parkinson-disease
#4
Ashley S Harms, Aaron D Thome, Zhaoqi Yan, Aubrey M Schonhoff, Gregory P Williams, Xinru Li, Yudong Liu, Hongwei Qin, Etty N Benveniste, David G Standaert
Accumulation of alpha-synuclein (α-syn) in the central nervous system (CNS) is a core feature of Parkinson disease (PD) that leads to activation of the innate immune system, production of inflammatory cytokines and chemokines, and subsequent neurodegeneration. Here, we used heterozygous reporter knock-in mice in which the first exons of the fractalkine receptor (CX3CR1) and of the C-C chemokine receptor type 2 (CCR2) are replaced with fluorescent reporters to study the role of resident microglia (CX3CR1+) and infiltrating peripheral monocytes (CCR2+), respectively, in the CNS...
November 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#5
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αMβ2, but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b(-/-) microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47(phox) and superoxide production...
November 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/29136779/juglanin-ameliorates-lps-induced-neuroinflammation-in-animal-models-of-parkinson-s-disease-and-cell-culture-via-inactivating-tlr4-nf-%C3%AE%C2%BAb-pathway
#6
Fang-Xue Zhang, Ren-Shi Xu
Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid β (Aβ) and p-Tau...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#7
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29024008/immunization-with-%C3%AE-synuclein-grp94-reshapes-peripheral-immunity-and-suppresses-microgliosis-in-a-chronic-parkinsonism-model
#8
Javier Villadiego, Adahir Labrador-Garrido, Jaime M Franco, Magdalena Leal-Lasarte, Erwin J De Genst, Christopher M Dobson, David Pozo, Juan J Toledo-Aral, Cintia Roodveldt
Neuroinflammation mediated by chronically activated microglia, largely caused by abnormal accumulation of misfolded α-synuclein (αSyn) protein, is known to contribute to the pathophysiology of Parkinson's disease (PD). In this work, based on the immunomodulatory activities displayed by particular heat-shock proteins (HSPs), we tested a novel vaccination strategy that used a combination of αSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used two different procedures, first, the adoptive transfer of splenocytes from αSyn/Grp94-immunized mice to recipient animals, and second, direct immunization with αSyn/Grp94, to study the effects in a chronic mouse MPTP-model of parkinsonism...
January 2018: Glia
https://www.readbyqxmd.com/read/28921554/dj-1-deficiency-impairs-autophagy-and-reduces-alpha-synuclein-phagocytosis-by-microglia
#9
Yuval Nash, Eran Schmukler, Dorit Trudler, Ronit Pinkas-Kramarski, Dan Frenkel
Parkinson's disease (PD) is a progressive neurodegenerative disorder, of which 1% of the hereditary cases are linked to mutations in DJ-1, an oxidative stress sensor. The pathological hallmark of PD is intercellular inclusions termed Lewy Bodies, composed mainly of α-Synuclein (α-Syn) protein. Recent findings have shown that α-Syn can be transmitted from cell to cell, suggesting an important role of microglia, as the main scavenger cells of the brain, in clearing α-Syn. We previously reported that the knock down (KD) of DJ-1 in microglia increased cells' neurotoxicity to dopaminergic neurons...
September 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28918943/vagus-nerve-stimulation-improves-locomotion-and-neuronal-populations-in-a-model-of-parkinson-s-disease
#10
Ariana Q Farrand, Kristi L Helke, Rebecca A Gregory, Monika Gooz, Vanessa K Hinson, Heather A Boger
BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. OBJECTIVE: To assess therapeutic potential of VNS in a PD model...
November 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28903781/transmission-of-%C3%AE-synuclein-containing-erythrocyte-derived-extracellular-vesicles-across-the-blood-brain-barrier-via-adsorptive-mediated-transcytosis-another-mechanism-for-initiation-and-progression-of-parkinson-s-disease
#11
Junichi Matsumoto, Tessandra Stewart, Lifu Sheng, Na Li, Kristin Bullock, Ning Song, Min Shi, William A Banks, Jing Zhang
Parkinson's disease (PD) pathophysiology develops in part from the formation, transmission, and aggregation of toxic species of the protein α-synuclein (α-syn). Recent evidence suggests that extracellular vesicles (EVs) may play a vital role in the transport of toxic α-syn between brain regions. Moreover, increasing evidence has highlighted the participation of peripheral molecules, particularly inflammatory species, which may influence or exacerbate the development of PD-related changes to the central nervous system (CNS), although detailed characterization of these species remains to be completed...
September 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28900002/modeling-parkinson-s-disease-pathology-by-combination-of-fibril-seeds-and-%C3%AE-synuclein-overexpression-in-the-rat-brain
#12
Poonam Thakur, Ludivine S Breger, Martin Lundblad, Oi Wan Wan, Bengt Mattsson, Kelvin C Luk, Virginia M Y Lee, John Q Trojanowski, Anders Björklund
Although a causative role of α-synuclein (α-syn) is well established in Parkinson's disease pathogenesis, available animal models of synucleinopathy do not replicate the full range of cellular and behavioral changes characteristic of the human disease. This study was designed to generate a more faithful model of Parkinson's disease by injecting human α-syn fibril seeds into the rat substantia nigra (SN), in combination with adenoassociated virus (AAV)-mediated overexpression of human α-syn, at levels that, by themselves, are unable to induce acute dopamine (DA) neurodegeneration...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28863860/discoidin-domain-receptor-inhibition-reduces-neuropathology-and-attenuates-inflammation-in-neurodegeneration-models
#13
Michaeline Hebron, Margo Peyton, Xiaoguang Liu, Xiaokong Gao, Ruochong Wang, Irina Lonskaya, Charbel E-H Moussa
The role of cell surface tyrosine kinase collagen-activated receptors known as discoidin domain receptors (DDRs) is unknown in neurodegenerative diseases. We detect up-regulation in DDRs level in post-mortem Alzheimer and Parkinson brains. Lentiviral shRNA knockdown of DDR1 and DDR2 reduces the levels of α-synuclein, tau, and β-amyloid and prevents cell loss in vivo and in vitro. DDR1 and DDR2 knockdown alters brain immunity and significantly reduces the level of triggering receptor expressed on myeloid cells (TREM)-2 and microglia...
October 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28836226/the-ketone-body-%C3%AE-hydroxybutyrate-does-not-inhibit-synuclein-mediated-inflammasome-activation-in-microglia
#14
Vandana Deora, Eduardo A Albornoz, Kevin Zhu, Trent M Woodruff, Richard Gordon
Parkinson's disease (PD) is recognized as the most common neurodegenerative movement disorder and results in debilitating motor deficits. The accumulation and spread of neurotoxic synuclein aggregates in the form of Lewy bodies is a key pathological feature of PD. Chronic activation of the NLRP3 inflammasome by protein aggregates is emerging as a major pathogenic mechanism in progressive neurodegenerative disorders and is considered an important therapeutic target. Recently the ketone body, β-hydroxy butyrate (BHB), was shown to efficiently inhibit the NLRP3 inflammasome in macrophages, and in vivo models of inflammatory disease...
December 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28827786/excess-%C3%AE-synuclein-compromises-phagocytosis-in-ipsc-derived-macrophages
#15
Walther Haenseler, Federico Zambon, Heyne Lee, Jane Vowles, Federica Rinaldi, Galbha Duggal, Henry Houlden, Katrina Gwinn, Selina Wray, Kelvin C Luk, Richard Wade-Martins, William S James, Sally A Cowley
To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827536/cellular-internalization-of-alpha-synuclein-aggregates-by-cell-surface-heparan-sulfate-depends-on-aggregate-conformation-and-cell-type
#16
Elisabet Ihse, Hodaka Yamakado, Xander M van Wijk, Roger Lawrence, Jeffrey D Esko, Eliezer Masliah
Amyloid aggregates found in the brain of patients with neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are thought to spread to increasingly larger areas of the brain through a prion-like seeding mechanism. Not much is known about which cell surface receptors may be involved in the cell-to-cell transfer, but proteoglycans are of interest due to their well-known propensity to interact with amyloid aggregates. In this study, we investigated the involvement of plasma membrane-bound heparan and chondroitin sulfate proteoglycans in cellular uptake of aggregates consisting of α-synuclein, a protein forming amyloid aggregates in Parkinson's disease...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774789/impaired-cbs-h2s-signaling-axis-contributes-to-mptp-induced-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#17
Yu-Qing Yuan, Ya-Li Wang, Bao-Shi Yuan, Xin Yuan, Xiao-Ou Hou, Jin-Song Bian, Chun-Feng Liu, Li-Fang Hu
Hydrogen sulfide (H2S), a novel neuromodulator, is linked to the pathogenesis of several neurodegenerative disorders. Exogenous application of H2S exerts neuroprotection via anti-inflammation and anti-oxidative stress in animal and cellular models of Parkinson's disease (PD). However, the role of endogenous H2S and the contribution of its various synthases in PD remain unclear. In the present study, we found a decline of plasma and striatal sulfide level in 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model...
January 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28769786/mild-inflammatory-profile-without-gliosis-in-the-c-rel-deficient-mouse-modeling-a-late-onset-parkinsonism
#18
Vanessa Porrini, Mariana Mota, Edoardo Parrella, Arianna Bellucci, Marina Benarese, Lara Faggi, Paolo Tonin, Pier F Spano, Marina Pizzi
The impact of neuroinflammation and microglial activation to Parkinson's disease (PD) progression is still debated. Post-mortem analysis of PD brains has shown that neuroinflammation and microgliosis are key features of end-stage disease. However, microglia neuroimaging studies and evaluation of cerebrospinal fluid (CSF) cytokines in PD patients at earlier stages do not support the occurrence of a pronounced neuroinflammatory process. PD animal models recapitulating the motor and non-motor features of the disease, and the slow and progressive neuropathology, can be of great advantage in understanding whether and how neuroinflammation associates with the onset of symptoms and neuronal loss...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#19
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28736195/allelic-difference-in-mhc2ta-confers-altered-microglial-activation-and-susceptibility-to-%C3%AE-synuclein-induced-dopaminergic-neurodegeneration
#20
Itzia Jimenez-Ferrer, Michael Jewett, Ashmita Tontanahal, Marina Romero-Ramos, Maria Swanberg
Parkinson's Disease (PD) is a complex and heterogeneous neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta and pathological intracellular accumulation of alpha-synuclein (α-syn). In the vast majority of PD patients, the disease has a complex etiology, defined by multiple genetic and environmental risk factors. Common genetic variants in the human leukocyte-antigen (HLA) region have been associated to PD risk and the carriage of these can double the risk to develop PD...
July 20, 2017: Neurobiology of Disease
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