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microglia neuroinflammation parkinson' disease

Ruth Hornedo-Ortega, Ana B Cerezo, Rocío M de Pablos, Stéphanie Krisa, Tristan Richard, M Carmen García-Parrilla, Ana M Troncoso
Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson's disease among others. The hallmark of brain neuroinflammation is the activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease...
2018: Frontiers in Cellular Neuroscience
C Starhof, K Winge, N H H Heegaard, K Skogstrand, S Friis, A Hejl
INTRODUCTION: Neuroinflammation has been established to be part of the neuropathological changes in Parkinson's disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP). METHODS: On a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-γ, IL-10, IL-18, IL-1β, IL-4, IL-6, TGF-β1, and TNF-α, among patients with PD (n = 46), MSA (n = 35), and PSP (n = 39) or controls (n = 31)...
November 3, 2018: Journal of Neuroinflammation
Richard Gordon, Eduardo A Albornoz, Daniel C Christie, Monica R Langley, Vinod Kumar, Susanna Mantovani, Avril A B Robertson, Mark S Butler, Dominic B Rowe, Luke A O'Neill, Anumantha G Kanthasamy, Kate Schroder, Matthew A Cooper, Trent M Woodruff
Parkinson's disease (PD) is characterized by a profound loss of dopaminergic neurons in the substantia nigra, accompanied by chronic neuroinflammation, mitochondrial dysfunction, and widespread accumulation of α-synuclein-rich protein aggregates in the form of Lewy bodies. However, the mechanisms linking α-synuclein pathology and dopaminergic neuronal death to chronic microglial neuroinflammation have not been completely elucidated. We show that activation of the microglial NLR family pyrin domain containing 3 (NLRP3) inflammasome is a common pathway triggered by both fibrillar α-synuclein and dopaminergic degeneration in the absence of α-synuclein aggregates...
October 31, 2018: Science Translational Medicine
Duraisamy Kempuraj, Govindhasamy Pushpavathi Selvakumar, Ramasamy Thangavel, Mohammad Ejaz Ahmed, Smita Zaheer, Keerthana Kuppamma Kumar, Anudeep Yelam, Harleen Kaur, Iuliia Dubova, Sudhanshu P Raikwar, Shankar S Iyer, Asgar Zaheer
Parkinson's disease (PD) is characterized by the presence of inflammation-mediated dopaminergic neurodegeneration in the substantia nigra. Inflammatory mediators from activated microglia, astrocytes, neurons, T-cells and mast cells mediate neuroinflammation and neurodegeneration. Administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induces PD like motor deficits in rodents. 1-methyl-4-phenylpyridinium (MPP+), a toxic metabolite of MPTP activates glial cells, neurons and mast cells to release neuroinflammatory mediators...
October 26, 2018: Journal of Alzheimer's Disease: JAD
Steven Vetel, Sophie Sérrière, Johnny Vercouillie, Jackie Vergote, Gabrielle Chicheri, Jean-Bernard Deloye, Frédéric Dollé, Sylvie Bodard, Claire Tronel, Lydie Nadal-Desbarats, Antoine Lefèvre, Patrick Emond, Sylvie Chalon
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6-hydroxydopamine was unilaterally delivered in 3 sites along the striatum. The degenerative process was assessed through in vivo Positron Emission Tomography (PET) imaging and in vitro autoradiographic quantitation of the striatal dopamine transporter (DAT) and immunostaining of tyrosine hydroxylase (TH)...
October 28, 2018: Synapse
Gemma Manich, Mireia Recasens, Tony Valente, Beatriz Almolda, Berta González, Bernardo Castellano
Microglia are considered to be the resident macrophages of the CNS and main effector of immune brain function. Due to their essential role in the regulation of neuroinflammatory response, microglia constitute an important target for neurological diseases, such as multiple sclerosis, Alzheimer's or Parkinson's disease. The communication between neurons and microglia contributes to a proper maintenance of homeostasis in the CNS. Research developed in the last decade has demonstrated that this interaction is mediated by "Off-signals" - molecules exerting immune inhibition - and "On signals" - molecules triggering immune activation...
October 24, 2018: Neuroscience
Thea P Lillethorup, Andreas N Glud, Aage K O Alstrup, Ove Noer, Erik H T Nielsen, Anna C Schacht, Natalie Landeck, Deniz Kirik, Dariusz Orlowski, Jens Christian H Sørensen, Doris J Doudet, Anne M Landau
Impairment of the ubiquitin proteasome system has been implicated in Parkinson's disease. We used positron emission tomography to investigate longitudinal effects of chronic intracerebroventricular exposure to the proteasome inhibitor lactacystin on monoaminergic projections and neuroinflammation. Göttingen minipigs were implanted in the cisterna magna with a catheter connected to a subcutaneous injection port. Minipigs were imaged at baseline and after cumulative doses of 200 and 400 μg lactacystin, respectively...
October 24, 2018: Scientific Reports
Andreas-Antonios Roussakis, Paola Piccini
Neuroinflammation is an important aspect of Parkinson's disease. The study of Parkinson's disease neuroinflammation is quite challenging and is accompanied by controversy. To date, molecular imaging studies have been targeting microglia and more recently astrocytes. In this review article, we discuss the findings from key PET studies with tracers specific for the translocator protein (microglia-specific) and novel evidence from the development of astrocyte-specific PET tracers. We also discuss evidence from pathology studies and in the animal model of Parkinson's disease that form the biological background of current and newer PET neuroinflammation tracers...
2018: International Review of Neurobiology
Kustrimovic Natasa, Marino Franca, Marco Cosentino
Parkinson's disease (PD) is the second most common neurodegenerative disorder among elderly population, and it is depicted by the degeneration of dopaminergic neurons in the midbrain which is progressive. Up to the present time, the precise cause remains ill-defined and the mechanism of neurons death indeterminate. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidences have been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD...
October 9, 2018: Current Medicinal Chemistry
Yong-Fei Zhao, Qiong-Zhang, Jian-Feng Zhang, Zhi-Yin Lou, Hen-Bing Zu, Zi-Gao Wang, Wei-Cheng Zeng, Kai-Yao, Bao-Guo Xiao
Aging is an inevitable physiological challenge occurring in organisms over time, and is also the most important risk factor of neurodegenerative diseases. In this study, we observed cellular and molecular changes of different age mice and LPS-induced Parkinson disease (PD) model. The results showed that behavioral performance and dopaminergic (DA) neurons were declined, accompanied by increased expression of pro-inflammatory factors (TLR2, p-NF-kB-p65, IL-1β and TNF-α), as well as pro-oxidative stress factor gp91phox in aged mice compared with young mice...
October 2018: Aging and Disease
Suzanne Hickman, Saef Izzy, Pritha Sen, Liza Morsett, Joseph El Khoury
The neuroimmune system is involved in development, normal functioning, aging, and injury of the central nervous system. Microglia, first described a century ago, are the main neuroimmune cells and have three essential functions: a sentinel function involved in constant sensing of changes in their environment, a housekeeping function that promotes neuronal well-being and normal operation, and a defense function necessary for responding to such changes and providing neuroprotection. Microglia use a defined armamentarium of genes to perform these tasks...
October 2018: Nature Neuroscience
Chuhyon Corwin, Anastasia Nikolopoulou, Allen L Pan, Mariela Nunez-Santos, Shankar Vallabhajosula, Peter Serrano, John Babich, Maria E Figueiredo-Pereira
BACKGROUND: Prostaglandins are products of the cyclooxygenase pathway, which is implicated in Parkinson's disease (PD). Limited knowledge is available on mechanisms by which prostaglandins contribute to PD neurodegeneration. To address this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2 is the most abundant prostaglandin in the brain, and the one that increases the most under pathological conditions. Moreover, PGJ2 is spontaneously derived from PGD2. METHODS: In this study, we determined in rats the impact of unilateral nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS), PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH)...
September 20, 2018: Journal of Neuroinflammation
Yousheng Mo, Erjin Xu, Renrong Wei, Baoluu Le, Lei Song, Dongli Li, Yonggen Chen, Xiaotian Ji, Shuhuan Fang, Jiangang Shen, Cong Yang, Qi Wang
Parkinson's disease (PD), the second most common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although the molecular mechanisms underlying dopaminergic neuronal degeneration in PD remain unclear, neuroinflammation is considered as the vital mediator in the pathogenesis and progression of PD. Bushen-Yizhi Formula (BSYZ), a traditional Chinese medicine, has been demonstrated to exert antineuroinflammation in our previous studies. However, it remains unclear whether BSYZ is effective for PD...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Francis Herman, Susan Westfall, Justin Brathwaite, Giulio M Pasinetti
Neurodegenerative disorders constitute a group of multifaceted conditions characterized by the progressive loss of neurons and synaptic connections consequent to a combination of specific genetic predispositions and stochastic stressors. The neuropathologies observed in both Alzheimer's and Parkinson's disease are in part attributed to compounding intrinsic and extrinsic environmental stressors, which we propose may be limited by the administration of specific grape derived phytochemicals and their metabolized derivatives, specifically polyphenols isolated from grape botanicals...
2018: Frontiers in Pharmacology
Gregory P Williams, Aubrey M Schonhoff, Asta Jurkuvenaite, Aaron D Thome, David G Standaert, Ashley S Harms
BACKGROUND: Parkinson's disease (PD) is characterized by intracellular alpha-synuclein (α-syn) inclusions, progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and activation of the innate and adaptive immune systems. Disruption of immune signaling between the central nervous system (CNS) and periphery, such as through targeting the chemokine receptor type 2 (CCR2) or the major histocompatibility complex II (MHCII), is neuroprotective in rodent models of PD, suggesting a key role for innate and adaptive immunity in disease progression...
August 30, 2018: Journal of Neuroinflammation
Neelima Gupta, Sukanya Shyamasundar, Radhika Patnala, Aparna Karthikeyan, Thiruma V Arumugam, Eng-Ang Ling, S Thameem Dheen
Chronic activation of microglia is the hallmark of numerous neuropathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The activated microglia perpetuate inflammation by releasing an array of pro-inflammatory and neurotoxic factors, which eventually exacerbate neurotoxicity and neurodegeneration upon chronic activation of these cells. However, under acute conditions, activated microglia elicit pro-inflammatory as well as anti-inflammatory responses that are associated with neuroprotection...
September 10, 2018: Expert Opinion on Therapeutic Targets
Katharine M von Herrmann, Lucas A Salas, Eileen M Martinez, Alison L Young, Joseph M Howard, Mary S Feldman, Brock C Christensen, Owen M Wilkins, Stephen L Lee, William F Hickey, Matthew C Havrda
Neuroinflammation is a well-characterized pathophysiology occurring in association with the progression of Parkinson's disease. Characterizing the cellular and molecular basis of neuroinflammation is critical to understanding its impact on the incidence and progression of PD and other neurologic disorders. Inflammasomes are intracellular pro-inflammatory pattern-recognition receptors capable of initiating and propagating inflammation. These cellular complexes are well characterized in the innate immune system and activity of the NLRP3 inflammasome has been reported in microglia...
2018: NPJ Parkinson's Disease
Hiroyuki Konishi, Hiroshi Kiyama
Microglia are activated after neuronal injury and in neurodegenerative diseases, and trigger neuroinflammation in the central nervous system (CNS). Microglia-derived neuroinflammation has both beneficial and detrimental effects on neurons. Because the timing and magnitude of microglial activation is thought to be a critical determinant of neuronal fate, understanding the molecular mechanisms underlying microglial activation is required to enable establishment of microglia-targeted therapies for neural diseases...
2018: Frontiers in Cellular Neuroscience
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons. The cell bodies of these neurons are present in the substantia nigra, with the nerve terminals being in the striatum. Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these. Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway...
September 2018: Neural Regeneration Research
Xu Jiang, Palanivel Ganesan, Thamaraiselvan Rengarajan, Dong-Kug Choi, Palanisamy Arulselvan
Pathogenesis of Parkinson's disease (PD) is undoubtedly a multifactorial phenomenon, with diverse etiological agents. Pro-inflammatory mediators act as a skew that directs disease progression during neurodegenerative diseases. Understanding the dynamics of inflammation and inflammatory mediators in preventing or reducing disease progression has recently gained much attention. Inflammatory neuro-degeneration is regulated via cytokines, chemokines, lipid mediators and immune cell subsets; however, individual cellular phenotypes in the Central Nervous System (CNS) acts in diverse ways whose persistent activation leads to unresolving inflammation often causing unfavorable outcomes in neurodegenerative disease like PD...
October 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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