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microglia neuroinflammation parkinson' disease

Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
October 11, 2016: Journal of Ethnopharmacology
Neal K Bennett, Rebecca Chmielowski, Dalia S Abdelhamid, Jonathan J Faig, Nicola Francis, Jean Baum, Zhiping P Pang, Kathryn E Uhrich, Prabhas V Moghe
Neuroinflammation, a common neuropathologic feature of neurodegenerative disorders including Parkinson disease (PD), is frequently exacerbated by microglial activation. The extracellular protein α-synuclein (ASYN), whose aggregation is characteristic of PD, remains a key therapeutic target, but the control of synuclein trafficking and aggregation within microglia has been challenging. First, we established that microglial internalization of monomeric ASYN was mediated by scavenger receptors (SR), CD36 and SRA1, and was rapidly accompanied by the formation of ASYN oligomers...
December 2016: Biomaterials
Zhaoqi Yan, Sara A Gibson, Jessica A Buckley, Hongwei Qin, Etty N Benveniste
The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity. Aberrant activation of the JAK/STAT pathway is evident in neuroinflammatory diseases such as Multiple Sclerosis and Parkinson's Disease. Innate immunity is the front line defender of the immune system and is composed of various cell types, including microglia, macrophages and neutrophils...
October 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Weidong Le, Junjiao Wu, Yu Tang
Microglia-mediated neuroinflammation is a hallmark of Parkinson's disease (PD). In the brains of patients with PD, microglia have both neurotoxic and neuroprotective effects, depending on their activation state. In this review, we focus on recent research demonstrating the neuroprotective role of microglia in PD. Accumulating evidence indicates that the protective mechanisms of microglia may result from their regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification, and microRNA regulation...
2016: Frontiers in Molecular Neuroscience
Giovanna Mulas, Elena Espa, Sandro Fenu, Saturnino Spiga, Giovanni Cossu, Elisabetta Pillai, Ezio Carboni, Gabriella Simbula, Dragana Jadžić, Fabrizio Angius, Stefano Spolittu, Barbara Batetta, Daniela Lecca, Andrea Giuffrida, Anna R Carta
Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear whether increased inflammation is specifically related to the dyskinetic outcome of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA infusion is associated with very low dyskinetic outcome in PD patients. We reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian rats, where dyskinetic responses and striatal neuroinflammation induced by chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared...
September 30, 2016: Experimental Neurology
Daniela Elgueta, María S Aymerich, Francisco Contreras, Andro Montoya, Marta Celorrio, Estefanía Rojo-Bustamante, Eduardo Riquelme, Hugo González, Mónica Vásquez, Rafael Franco, Rodrigo Pacheco
Neuroinflammation involves the activation of glial cells, which is associated to the progression of neurodegeneration in Parkinson's disease. Recently, we and other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are completely refractory to neuroinflammation and consequent neurodegeneration associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we examined the therapeutic potential and underlying mechanism of a D3R-selective antagonist, PG01037, in mice intoxicated with a chronic regime of administration of MPTP and probenecid (MPTPp)...
September 28, 2016: Neuropharmacology
Alana Hoffmann, Benjamin Ettle, Ariane Bruno, Anna Kulinich, Anna-Carin Hoffmann, Julia von Wittgenstein, Jürgen Winkler, Wei Xiang, Johannes C M Schlachetzki
Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are defined by the presence of intracellular alpha-synuclein aggregates in neurons and/or oligodendrocytes. In addition, post mortem tissue analysis revealed profound changes in microglial morphology, indicating microglial activation and neuroinflammation. Thus, alpha-synuclein may directly activate microglia, leading to increased production of key pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), which in turn modulates the disease progression...
October 28, 2016: Biochemical and Biophysical Research Communications
Qimei Wu, Xiaoyu Yang, Yu Zhang, Lei Zhang, Linyin Feng
Daily stress is associated with increased risk for various diseases, and numerous studies have provided evidence that environmental stress leads to deleterious effects on the central nervous system. However, it remains unclear whether chronic stress exacerbates the progression of Parkinson's disease (PD). To investigate this hypothesis, we determined the effect of chronic mild stress (CMS) on the pathogenesis of PD in a transgenic mice line that overexpresses the human A53T mutant α-synuclein (A53T Tg mice)...
November 2016: Experimental Neurology
Claire Hoenen, Audrey Gustin, Cindy Birck, Mélanie Kirchmeyer, Nicolas Beaume, Paul Felten, Luc Grandbarbe, Paul Heuschling, Tony Heurtaux
Parkinson's disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point mutations of the gene encoding the α-synuclein protein cause inherited forms of PD. There are currently six known point mutations that result in familial PD. Oxidative stress and neuroinflammation have also been described as early events associated with dopaminergic neuronal degeneration in PD. Though it is known that microglia are activated by wild-type α-synuclein, little is known about its mutated forms and the signaling cascades responsible for this microglial activation...
2016: PloS One
Elaine Del-Bel, Mariza Bortolanza, Maurício Dos-Santos-Pereira, Keila Bariotto, Rita Raisman-Vozari
Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease...
December 2016: Synapse
Eunju Leem, Kyoung Hoon Jeong, So-Yoon Won, Won-Ho Shin, Sang Ryong Kim
Although accumulating evidence suggests that microglia-mediated neuroinflammation may be crucial for the initiation and progression of Parkinson's disease (PD), and that the control of neuroinflammation may be a useful strategy for preventing the degeneration of nigrostriatal dopaminergic (DA) projections in the adult brain, it is still unclear what kinds of endogenous biomolecules initiate microglial activation, consequently resulting in neurodegeneration. Recently, we reported that the increase in the levels of prothrombin kringle-2 (pKr-2), which is a domain of prothrombin that is generated by active thrombin, can lead to disruption of the nigrostriatal DA projection...
August 2016: Experimental Neurobiology
Mei-Li Díaz-Hung, Arianna Yglesias-Rivera, Luis Fernando Hernández-Zimbrón, Sandra Orozco-Suárez, Jenny Laura Ruiz-Fuentes, Alexis Díaz-García, Rilda León-Martínez, Lisette Blanco-Lezcano, Nancy Pavón-Fuentes, Lourdes Lorigados-Pedre
Glutathione (GSH) deficiency has been identified as an early event in the progression of Parkinson's disease. However, the role of GSH in the etiology and pathogenesis of this neurodegenerative disorder is not well established. The aim of this study is to assess the effect of transient GSH depletion in the substantia nigra pars compacta (SNpc) on neuroinflammation after the injection of a single dose of l-buthionine sulfoximine (BSO) into the SNpc of male Sprague-Dawley rats. The results showed that BSO treatment stimulates microglia (p<0...
October 29, 2016: Neuroscience
Hayate Javed, Sheikh Azimullah, Salema B Abul Khair, Shreesh Ojha, M Emdadul Haque
BACKGROUND: Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; however, accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. Current medications for PD can only improve its symptoms, but are unable to halt its progressive nature. Although many therapeutic approaches are available, new drugs are urgently needed for the treatment of PD...
2016: BMC Neuroscience
Hayate Javed, Sheikh Azimullah, M Emdadul Haque, Shreesh K Ojha
The cannabinoid type two receptors (CB2), an important component of the endocannabinoid system, have recently emerged as neuromodulators and therapeutic targets for neurodegenerative diseases including Parkinson's disease (PD). The downregulation of CB2 receptors has been reported in the brains of PD patients. Therefore, both the activation and the upregulation of the CB2 receptors are believed to protect against the neurodegenerative changes in PD. In the present study, we investigated the CB2 receptor-mediated neuroprotective effect of β-caryophyllene (BCP), a naturally occurring CB2 receptor agonist, in, a clinically relevant, rotenone (ROT)-induced animal model of PD...
2016: Frontiers in Neuroscience
Yan-Xia Yu, Yi-Pei Li, Feng Gao, Qing-Song Hu, Yan Zhang, Dong Chen, Guang-Hui Wang
AIM: Increasing evidence has shown that environmental factors such as rotenone and paraquat induce neuroinflammation, which contributes to the pathogenesis of Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying the repression by menaquinone-4 (MK-4), a subtype of vitamin K2, of rotenone-induced microglial activation in vitro. METHODS: A microglial cell line (BV2) was exposed to rotenone (1 μmol/L) with or without MK-4 treatment...
September 2016: Acta Pharmacologica Sinica
Xiaojin Shi, Yu-Hua Chen, Hao Liu, Hong-Dang Qu
Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via i.p. injection for five consecutive days to induce the mouse model of PD...
September 2016: Molecular Medicine Reports
Dimitry A Chistiakov, Alexander A Chistiakov
Exosomes play a key role in delivery of various biological material and complex signals from one cell to another at long distances. These small extracellular vehicles are involved in mediating multiple physiological and pathogenic processes. In neurodegenerative diseases such as Parkinson's disease (PD), exosomes contribute to disease propagation through transferring misfolded proteins from affected cells to normal cells. In PD, progressive degeneration of neurons arises from the extensive accumulation of toxic forms of α-synuclein in the cytoplasm...
July 29, 2016: Acta Neurologica Belgica
Parakalan Rangarajan, Aparna Karthikeyan, S T Dheen
Chronic neuroinflammation is a pathological feature of a number of central nervous system (CNS) diseases and is mediated by sustained activation of microglial cells, the innate immune cells of the CNS. Studies have mainly focused on identifying the molecular and epigenetic mechanisms of microglial activation. This is crucial in designing therapeutic strategies for neuropathologies in which prolonged microglial activation is known to exacerbate disease condition. In recent years, increasing evidence show that naturally occurring compounds present in regular diet could function as "nutraceuticals," arresting microglial activation, and thus conferring neuroprotection...
September 2016: Neuromolecular Medicine
Jun Wang, Wang-Yang Wu, Huan Huang, Wei-Zu Li, Han-Qing Chen, Yan-Yan Yin
Neuroinflammation has been reported to be involved in the pathogenesis of Parkinson's disease (PD). Inhibition of microglia-mediated neuroinflammation might be a potential strategy for PD treatment. Biochanin A, is an O-methylated isoflavone, classified as a kind of phytoestrogens due to its chemical structure that is similar to mammalian estrogens. It has been found to possess antifibrotic, antiapoptotic, and antioxidant effects. In the present study, we investigated the neuroprotective effects of biochanin A on lipopolysaccharide (LPS)-induced dopaminergic neurons damage both in vivo and in vitro and the related molecular mechanisms...
October 2016: Neurotoxicity Research
Yuqi Huang, Zhe Zhao, Xiaoli Wei, Yong Zheng, Jianqiang Yu, Jianquan Zheng, Liyun Wang
BACKGROUND: Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved...
2016: Journal of Neuroinflammation
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