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microglia neuroinflammation parkinson' disease

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
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
Matthew L Neal, Alexa M Boyle, Kevin M Budge, Fayez F Safadi, Jason R Richardson
BACKGROUND: Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia...
March 8, 2018: Journal of Neuroinflammation
Liyan Hou, Yuning Che, Fuqiang Sun, Qingshan Wang
Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model...
March 5, 2018: Amino Acids
Matthew J Benskey, Rhyomi C Sellnow, Ivette M Sandoval, Caryl E Sortwell, Jack W Lipton, Fredric P Manfredsson
Human studies and preclinical models of Parkinson's disease implicate the involvement of both the innate and adaptive immune systems in disease progression. Further, pro-inflammatory markers are highly enriched near neurons containing pathological forms of alpha synuclein (α-syn), and α-syn overexpression recapitulates neuroinflammatory changes in models of Parkinson's disease. These data suggest that α-syn may initiate a pathological inflammatory response, however the mechanism by which α-syn initiates neuroinflammation is poorly understood...
2018: Frontiers in Molecular Neuroscience
Francesca L'Episcopo, Cataldo Tirolo, Maria F Serapide, Salvatore Caniglia, Nunzio Testa, Loredana Leggio, Silvia Vivarelli, Nunzio Iraci, Stefano Pluchino, Bianca Marchetti
Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors...
2018: Frontiers in Aging Neuroscience
Xiuli Jiang, Xiaoli Wang, Miao Tuo, Jiangnan Ma, Anmu Xie
Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1...
February 22, 2018: Neuroscience Letters
Qin Rui, Haibo Ni, Di Li, Rong Gao, Gang Chen
The leucine-rich repeat kinase 2 (LRRK2) gene and α-synuclein gene (SNCA) are the key influence factors of Parkinson's disease (PD). It is reported that dysfunction of LRRK2 may influence the accumulation of α-synuclein and its pathology to alter cellular functions and signaling pathways by the kinase activation of LRRK2. The accumulation of α-synuclein is one of the main stimulants of microglias acitiviton. Microglias are macrophages resided in the brain, and activation of microglials is believed to contribute to neuroinflammation and neuronal death in PD...
February 22, 2018: Current Neuropharmacology
Meng-Fei Sun, Ying-Li Zhu, Zhi-Lan Zhou, Xue-Bing Jia, Yi-Da Xu, Qin Yang, Chun Cui, Yan-Qin Shen
Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs)...
February 19, 2018: Brain, Behavior, and Immunity
Namkwon Kim, Hyung-Seok Yoo, Yeon-Joo Ju, Myung Sook Oh, Kyung-Tae Lee, Kyung-Soo Inn, Nam-Jung Kim, Jong Kil Lee
Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model...
March 1, 2018: Biomolecules & Therapeutics
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
Manru Ren, Ying Guo, Xinbing Wei, Shaoqi Yan, Yue Qin, Xiumei Zhang, Fan Jiang, Haiyan Lou
Triggering receptor expressed on myeloid cells-2 (TREM2) was a newly identified receptor expressed on microglia. Several observations support the hypothesis that TREM2 variation may confer susceptibility to Parkinson's disease (PD). Therefore, in this paper, we explored the role of TREM2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results revealed that overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo...
January 27, 2018: Experimental Neurology
Cristina Agliardi, Franca Rosa Guerini, Milena Zanzottera, Giulio Riboldazzi, Roberta Zangaglia, Giorgio Bono, Carlo Casali, Cherubino Di Lorenzo, Claudio Pacchetti, Raffaello Nemni, Mario Clerici
The etiology of sporadic Parkinson's disease is (PD) still not understood but it is believed that a complex interplay between environmental and genetic factors could trigger the pathology. Pro-inflammatory TNF-α is released by activated microglia and is up-regulated in the brain and cerebrospinal fluid of PD patients; TNF-α modulates neuroinflammation and can activate the molecular mechanisms that lead to neurotoxicity and neuronal death. We analyzed two functional SNPs within the TNF-α gene promoter (rs361525 and rs1800629) in 354 Italian PD patients and 443 healthy controls (HC)...
February 15, 2018: Journal of the Neurological Sciences
Xiaoxia Yang, Honglei Ren, Kristofer Wood, Minshu Li, Shenfeng Qiu, Fu-Dong Shi, Cungen Ma, Qiang Liu
The activation of microglia and the various substances they produce have been linked to the pathologic development of Parkinson's disease (PD), but the precise role of microglia in PD remains to be defined. The survival of microglia depends on colony-stimulating factor 1 receptor (CSF1R) signaling, and CSF1R inhibition results in rapid elimination of microglia in the central nervous system. Using a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, we showed that the depletion of microglia via the CSF1R inhibitor PLX3397 exacerbated the impairment of locomotor activities and the loss of dopaminergic neurons...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Emily L Gill, Shreya Raman, Richard A Yost, Timothy J Garrett, Vinata Vedam-Mai
Microglia are the resident immune effector cells of the central nervous system. They account for approximately 10- 15% of all cells found in the brain and spinal cord, acting as macrophages, sensing and engaging in phagocytosis to eliminate toxic proteins. Microglia are dynamic and can change their morphology in response to cues from their milieu. Parkinson's disease is a neurodegenerative disease, associated with reactive gliosis, neuroinflammation, and oxidative stress. It is thought that Parkinson's disease is caused by the accumulation of abnormally folded alpha-synuclein protein, accompanied by persistent neuroinflammation, oxidative stress, and subsequent neuronal injury/death...
January 25, 2018: ACS Chemical Neuroscience
Qing Yu, Qiaoying Huang, Xiaoxiao Du, Shao Xu, Mingtao Li, Shanshan Ma
The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction of Egr-1 in the SNpc but not in the striatum...
January 11, 2018: Experimental Neurology
Longping Yao, Yongyi Ye, Hengxu Mao, Fengfei Lu, Xiaozheng He, Guohui Lu, Shizhong Zhang
BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disorder that is characterised by selective loss of midbrain dopaminergic (DA) neurons. Chronic inflammation of the central nervous system is mediated by microglial cells and plays a critical role in the pathological progression of PD. Brain-specific microRNA-124 (miR-124) expression is significantly downregulated in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD...
January 12, 2018: Journal of Neuroinflammation
Liuke Sun, Ruifang Shen, Sandeep K Agnihotri, Yun Chen, Zhiwei Huang, Hansruedi Büeler
Neuroinflammation is involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. We show that lack of PINK1- a mitochondrial kinase linked to recessive familial PD - leads to glia type-specific abnormalities of innate immunity. PINK1 loss enhances LPS/IFN-γ stimulated pro-inflammatory phenotypes of mixed astrocytes/microglia (increased iNOS, nitric oxide and COX-2, reduced IL-10) and pure astrocytes (increased iNOS, nitric oxide, TNF-α and IL-1β), while attenuating expression of both pro-inflammatory (TNF-α, IL-1β) and anti-inflammatory (IL-10) cytokines in microglia...
January 10, 2018: Scientific Reports
Teresa Trotta, Maria Antonietta Panaro, Antonia Cianciulli, Giorgio Mori, Adriana Di Benedetto, Chiara Porro
Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells...
January 3, 2018: Biochemical Pharmacology
Lalita Subedi, Oh Wook Kwon, Chaeho Pak, Goeun Lee, Kangwoo Lee, Hakwon Kim, Sun Yeou Kim
BACKGROUND: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. RESULTS: Out of 13 derivatives, compound 3 [4,4'-(1E,1'E,3E,3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12...
December 28, 2017: BMC Neuroscience
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