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https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#1
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29779175/anthocyanins-improve-hippocampus-dependent-memory-function-and-prevent-neurodegeneration-via-jnk-akt-gsk3%C3%AE-signaling-in-lps-treated-adult-mice
#2
Muhammad Sohail Khan, Tahir Ali, Min Woo Kim, Myeung Hoon Jo, Jong Il Chung, Myeong Ok Kim
Microglia plays a critical role in the brain and protects neuronal cells from toxins. However, over-activation of microglia leads to deleterious effects. Lipopolysaccharide (LPS) has been reported to affect neuronal cells via activation of microglia as well as directly to initiate neuroinflammation. In the present study, we evaluated the anti-inflammatory and anti-oxidative effect of anthocyanins against LPS-induced neurotoxicity in an animal model and in cell cultures. Intraperitoneal injections of LPS (250 μg/kg/day for 1 week) induce ROS production and promote neuroinflammation and neurodegeneration which ultimately leads to memory impairment...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29775624/characterization-and-comparative-analysis-of-a-new-mouse-microglial-cell-model-for-studying-neuroinflammatory-mechanisms-during-neurotoxic-insults
#3
Souvarish Sarkar, Emir Malovic, Deeksha Sarda, Vivek Lawana, Dharmin Rokad, Huajun Jin, Vellareddy Anantharam, Arthi Kanthasamy, Anumantha G Kanthasamy
Microglia are the first responders of the central nervous system, acting as the key modulators of neuroinflammation observed during neurotoxic insults as well as in the pathophysiology of several neurodegenerative disorders including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD). The number of publications on microglia has increased steadily throughout the past decade because of immense interests in the neuroinflammation that precedes the neurodegenerative process. To study microglial biology and its role in modulating neuroinflammation, immortalized microglial cell lines derived from mice, rats, and humans have been developed...
May 15, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29759145/thymoquinone-increases-the-expression-of-neuroprotective-proteins-while-decreasing-the-expression-of-pro-inflammatory-cytokines-and-the-gene-expression-nf%C3%AE%C2%BAb-pathway-signaling-targets-in-lps-ifn%C3%AE-activated-bv-2-microglia-cells
#4
Makini K Cobourne-Duval, Equar Taka, Patricia Mendonca, Karam F A Soliman
Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29755324/effect-of-chronic-oxidative-stress-on-neuroinflammatory-response-mediated-by-cd4-t-cells-in-neurodegenerative-diseases
#5
REVIEW
Helena Solleiro-Villavicencio, Selva Rivas-Arancibia
In a state of oxidative stress, there is an increase of reactive species, which induce an altered intracellular signaling, leading to dysregulation of the inflammatory response. The inability of the antioxidant defense systems to modulate the proinflammatory response is key to the onset and progression of neurodegenerative diseases. The aim of this work is to review the effect of the state of oxidative stress on the loss of regulation of the inflammatory response on the microglia and astrocytes, the induction of different CD4+ T cell populations in neuroinflammation, as well as its role in some neurodegenerative diseases...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29720230/urate-inhibits-microglia-activation-to-protect-neurons-in-an-lps-induced-model-of-parkinson-s-disease
#6
Li-Hui Bao, Ya-Nan Zhang, Jian-Nan Zhang, Li Gu, Hui-Min Yang, Yi-Ying Huang, Ning Xia, Hong Zhang
BACKGROUND: Multiple risk factors contribute to the progression of Parkinson's disease, including oxidative stress and neuroinflammation. Epidemiological studies have revealed a link between higher urate level and a lower risk of developing PD. However, the mechanistic basis for this association remains unclear. Urate protects dopaminergic neurons from cell death induced by oxidative stress. Here, we investigated a novel role of urate in microglia activation in a lipopolysaccharide (LPS)-induced PD model...
May 2, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29716614/lewy-body-like-alpha-synuclein-inclusions-trigger-reactive-microgliosis-prior-to-nigral-degeneration
#7
Megan F Duffy, Timothy J Collier, Joseph R Patterson, Christopher J Kemp, Kelvin C Luk, Malú G Tansey, Katrina L Paumier, Nicholas M Kanaan, Luke D Fischer, Nicole K Polinski, Olivia L Barth, Jacob W Howe, Nishant N Vaikath, Nour K Majbour, Omar M A El-Agnaf, Caryl E Sortwell
BACKGROUND: Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as a platform to investigate the role of neuroinflammation in degeneration in PD. However, due to features of the previously available PD models, interpretations of the role of neuroinflammation as a contributor to or a consequence of neurodegeneration have remained elusive. In the present study, we investigated the temporal relationship of neuroinflammation in a model of synucleinopathy following intrastriatal injection of pre-formed alpha-synuclein fibrils (α-syn PFFS)...
May 1, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29678518/pattern-recognition-receptors-mediate-pro-inflammatory-effects-of-extracellular-mitochondrial-transcription-factor-a-tfam
#8
Stephanie M Schindler, Matthew G Frank, Jessica L Annis, Steven F Maier, Andis Klegeris
Neuroinflammation is a common pathogenic mechanism for a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Microglia, the immune cells of the brain, contribute to the onset and progression of the neuroinflammation observed in these diseases. Microglia become activated and initiate an inflammatory response by interacting with a diverse set of molecules, including the group of endogenous proteins released upon cell damage, termed damage-associated molecular patterns (DAMPs)...
April 17, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29667931/ave0991-a-nonpeptide-analogue-of-ang-1-7-attenuates-aging-related-neuroinflammation
#9
Teng Jiang, Liu-Jun Xue, Yang Yang, Qing-Guang Wang, Xiao Xue, Zhou Ou, Qing Gao, Jian-Quan Shi, Liang Wu, Ying-Dong Zhang
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7)...
April 17, 2018: Aging
https://www.readbyqxmd.com/read/29665074/parkin-deficiency-modulates-nlrp3-inflammasome-activation-by-attenuating-an-a20-dependent-negative-feedback-loop
#10
François Mouton-Liger, Thibault Rosazza, Julia Sepulveda-Diaz, Amélie Ieang, Sidi-Mohamed Hassoun, Emilie Claire, Graziella Mangone, Alexis Brice, Patrick P Michel, Jean-Christophe Corvol, Olga Corti
Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways. We report here an exacerbation of NLRP3 inflammasome activation by specific inducers in microglia and bone marrow-derived macrophages from Park2-/- and Pink1-/- mice...
April 17, 2018: Glia
https://www.readbyqxmd.com/read/29649522/triptolide-up-regulates-metabotropic-glutamate-receptor-5-to-inhibit-microglia-activation-in-the-lipopolysaccharide-induced-model-of-parkinson-s-disease
#11
Yi-Ying Huang, Qian Zhang, Jian-Nan Zhang, Ya-Nan Zhang, Li Gu, Hui-Min Yang, Ning Xia, Xiao-Min Wang, Hong Zhang
Metabotropic glutamate receptor (mGlu)5 regulates microglia activation, which contributes to inflammation. However, the role of mGlu5 in neuroinflammation associated with Parkinson's disease (PD) remains unclear. Triptolide (T10) exerts potent immunosuppressive and anti-inflammatory effects and protects neurons by inhibiting microglia activation. In this study, we investigated the role of mGlu5 in the anti-inflammatory effect of T10 in a lipopolysaccharide (LPS)-induced PD model. In cultured BV2 cells and primary microglia, blocking mGlu5 activity or knocking down its expression abolished T10-inhibited release of proinflammatory cytokines induced by LPS...
April 9, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29626798/synthesis-and-biological-evaluation-of-clovamide-analogues-as-potent-anti-neuroinflammatory-agents-in-vitro-and-in-vivo
#12
Xiao-Long Hu, Jun Lin, Xian-Yu Lv, Jia-Hao Feng, Xiao-Qi Zhang, Hao Wang, Wen-Cai Ye
A series of clovamide analogues, namely, 1a-13a and 1b-13b, was synthesized and evaluated for their anti-neuroinflammatory activities using BV-2 microglia cells. Among these compounds, six (1b, 4b-8b) showed NO inhibition with no or weak cytotoxicity (CC50  > 100 μM), especially 4b, and showed an IC50 value of 2.67 μM. Enzyme activity and docking assay revealed that the six compounds, especially 4b, target inducible NO synthase (iNOS) and exhibit potent inhibitory effects on iNOS with IC50 values ranging from 1...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29624735/cx3cr1-deficiency-exacerbates-alpha-synuclein-a53t-induced-neuroinflammation-and-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#13
Sara Castro-Sánchez, Ángel J García-Yagüe, Tresa López-Royo, Maria Casarejos, José Luis Lanciego, Isabel Lastres-Becker
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the substantia nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant is alpha-synuclein (α-SYN). Mutations of the gene that codes for α-SYN (SNCA), such as the A53T mutation, and duplications of the gene generate cases of PD with autosomal dominant inheritance. As a result of the association of inflammation with the neurodegeneration of PD, we analyzed whether overexpression of wild-type α-SYN (α-SYNWT ) or mutated α-SYN (α-SYNA53T ) are involved in the neuronal dopaminergic loss and inflammation process, along with the role of the chemokine fractalkine (CX3CL1) and its receptor (CX3CR1)...
April 6, 2018: Glia
https://www.readbyqxmd.com/read/29621548/trem2-modulates-microglia-phenotypes-in-the-neuroinflammation-of-parkinson-s-disease
#14
Youwen Zhang, Shujun Feng, Kun Nie, Yan Li, Yuyuan Gao, Rong Gan, Limin Wang, Bing Li, Xuegang Sun, Lijuan Wang, Yuhu Zhang
Neuroinflammation and overactivated microglia underlies the pathogenesis of Parkinson's disease (PD). Furthermore, microglia could polarize into classic inflammatory M1 and immunosuppressive M2 phenotype. Thus, inhibiting the overactivated inflammatory M1 microglia by promoting the transformation of microglia to the protective M2 phenotype provides potential therapy for PD, but the mechanism that modulates microglia polarization remains unknown. Triggering receptor expressed on myeloid cells-2 (TREM2) is a recently identified immune receptor expressed by the microglia in the brain...
April 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29618972/an-inflammation-centric-view-of-neurological-disease-beyond-the-neuron
#15
REVIEW
Stephen D Skaper, Laura Facci, Morena Zusso, Pietro Giusti
Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system ("neuroinflammation"), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29611482/potential-use-of-nanomedicine-for-the-anti-inflammatory-treatment-of-neurodegenerative-diseases
#16
Maria Dolores Cayero-Otero, Ana M Espinosa-Oliva, Antonio J Herrera, Irene Garcia-Dominguez, Mercedes Fernandez-Arevalo, Lucia Martin-Banderas, Rocio M de Pablos
Neurodegenerative diseases, like Alzheimer´s and Parkinson´s disease, are a group of disorders that have in common their increasingly high prevalence along with the shortage of effective treatments. In addition, the scientific community faces the challenge of getting the drugs used in these treatments to cross the blood-brain barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. Hence, researchers across multiple disciplines are working together in order to improve the ability of therapeutics to penetrate the BBB...
April 2, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29576855/tetrahydroxystilbene-glucoside-produces-neuroprotection-against-6-ohda-induced-dopamine-neurotoxicity
#17
Chun Huang, Fengqin Lin, Guoqing Wang, Disheng Lu, Qin Wu, Jie Liu, Jingshan Shi, Feng Zhang
Parkinson's disease (PD) was one of the most common neurodegenerative diseases with a slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation was identified to be an important contributor to PD pathogenesis with the hallmark of microglia activation. Tetrahydroxystilbene glucoside (TSG) was the main active component extracted from Polygonum multiflorum and held amounts of pharmacological activities including antioxidant, free radical-scavenging, anti-inflammation, and cardioprotective properties...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29568078/taurine-protects-dopaminergic-neurons-in-a-mouse-parkinson-s-disease-model-through-inhibition-of-microglial-m1-polarization
#18
Yuning Che, Liyan Hou, Fuqiang Sun, Cong Zhang, Xiaofang Liu, Fengyuan Piao, Dan Zhang, Huihua Li, Qingshan Wang
Microglia-mediated neuroinflammation is implicated in multiple neurodegenerative disorders, including Parkinson's disease (PD). Hence, the modulatioein of sustained microglial activation may have therapeutic potential. This study is designed to test the neuroprotective efficacy of taurine, a major intracellular free β-amino acid in mammalian tissues, by using paraquat and maneb-induced PD model. Results showed that mice intoxicated with paraquat and maneb displayed progressive dopaminergic neurodegeneration and motor deficits, which was significantly ameliorated by taurine...
March 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29541852/neuroinflammation-in-l-dopa-induced-dyskinesia-beyond-the-immune-function
#19
REVIEW
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29534526/peiminine-protects-dopaminergic-neurons-from-inflammation-induced-cell-death-by-inhibiting-the-erk1-2-and-nf-%C3%AE%C2%BAb-signalling-pathways
#20
Guangxin Chen, Juxiong Liu, Liqiang Jiang, Xin Ran, Dewei He, Yuhang Li, Bingxu Huang, Wei Wang, Dianfeng Liu, Shoupeng Fu
Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation...
March 12, 2018: International Journal of Molecular Sciences
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