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astrocytes and PD

Takuma Ohmichi, Masato Mitsuhashi, Harutsugu Tatebe, Takashi Kasai, Omar M Ali El-Agnaf, Takahiko Tokuda
INTRODUCTION: There is still a substantial unmet need for blood-based biomarkers to make an objective diagnosis of Parkinson's disease (PD) and the parkinsonism-plus syndromes. This study is aimed to determine whether enumeration of brain-derived exosomes (BDEs) in plasma is informative in the diagnosis of those diseases. METHODS: We have developed a specific method to enumerate the plasma levels of neuron-derived, astrocyte-derived, and oligodendrocyte-derived exosomes (NDEs, ADEs and ODEs, respectively), and quantified them individually in patients with PD (n = 15), multiple system atrophy (MSA, n = 15), progressive supranuclear palsy (PSP, n = 7) and disease controls (n = 15)...
November 20, 2018: Parkinsonism & related Disorders
Mona Dehhaghi, Vanessa Tan, Benjamin Heng, Fatemeh Mohammadipanah, Gilles J Guillemin
Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. In the present study, we evaluated the effects of myxobacterial extracts on hydrogen peroxide (H2 O2 ) mediated toxicity on primary human astrocytes...
November 26, 2018: Neuroscience
Sumit Sarkar, Edward Lu, James Raymick, Joseph Hanig, Qiang Gu
BACKGROUND: Parkinson disease (PD) is one of the most debilitating disorder of the elderly where dopaminergic neurons of the midbrain especially in the substantia nigra (SNc) are damaged. Dopaminergic neurons are synthesized in the midbrain project to the striatum (Caudate-putamen-CPU). Few evidence have suggested that the extracellular signal-regulated kinase ½ (ERK ½) in the brain is activated after 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure, to our knowledge no study has yet been done to demonstrate whether such activation occurs in neurons or in glia...
November 23, 2018: Current Neurovascular Research
Paulina Troncoso-Escudero, Alejandra Parra, Melissa Nassif, Rene L Vidal
Neuroinflammation is one of the most important processes involved in the pathogenesis of Parkinson's disease (PD). The current concept of neuroinflammation comprises an inflammation process, which occurs in the central nervous system due to molecules released from brain-resident and/or blood-derived immune cells. Furthermore, the evidence of the contribution of systemic delivered molecules to the disease pathogenesis, such as the gut microbiota composition, has been increasing during the last years. Under physiological conditions, microglia and astrocytes support the well-being and well-function of the brain through diverse functions, including neurotrophic factor secretion in both intact and injured brain...
2018: Frontiers in Neurology
Ying-Li Zhu, Meng-Fei Sun, Xue-Bing Jia, Kun Cheng, Yi-Da Xu, Zhi-Lan Zhou, Pei-Hao Zhang, Chen-Meng Qiao, Chun Cui, Xue Chen, Xu-Sheng Yang, Yan-Qin Shen
Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii, Engelhardia roxburghiana, Smilax corbularia and Erythroxylum gonocladum, and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i...
November 9, 2018: International Immunopharmacology
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...
2018: Journal of Alzheimer's Disease: JAD
Bernd L Fiebich, Carla Ribeiro Alvares Batista, Soraya Wilke Saliba, Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira
Toll-like receptors (TLRs) are a group of receptors widely distributed in the organism. In the central nervous system, they are expressed in neurons, astrocytes and microglia. Although their involvement in immunity is notorious, different articles have demonstrated their roles in physiological and pathological conditions, including neurodegeneration. There is increasing evidence of an involvement of TLRs, especially TLR2, 4 and 9 in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS)...
2018: Frontiers in Cellular Neuroscience
Xing-Zhi Guo, Chang Shan, Yan-Fang Hou, Geng Zhu, Bei Tao, Li-Hao Sun, Hong-Yan Zhao, Guang Ning, Sheng-Tian Li, Jian-Min Liu
Osteoblasts derived osteocalcin (OCN) is recently reported to be involved in dopaminergic neuronal development. As dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), we investigated whether OCN could exert protective effects on 6-hydroxydopamine (6-OHDA)-induced PD rat model. Our data showed that the OCN level in the cerebrospinal fluid (CSF) in PD rat models was significantly lower than that in controls. Intervention with OCN could improve the behavioral dysfunction in PD rat models and reduce the tyrosine hydroxylase (TH) loss in the nigrostriatal system...
2018: Frontiers in Molecular Neuroscience
Katarzyna Kuter, Łukasz Olech, Urszula Głowacka, Martyna Paleczna
Glial pathology precedes symptoms of Parkinson's disease (PD) and multiple other neurodegenerative diseases. Prolonged impairment of astrocytic functions could increase the vulnerability of dopaminergic neurons in the substantia nigra (SN), accelerate their degeneration and affect ability to compensate for partial degeneration at the presymptomatic stages of the disease. The aim of this study was to investigate the astrocyte depletion in the SN, its impact on the dopaminergic system functioning and multiple markers of energy metabolism during the early stages of neurodegeneration and compensation...
October 8, 2018: Journal of Neurochemistry
Yingjun Liu, Silvia Sorce, Mario Nuvolone, Julie Domange, Adriano Aguzzi
Prion diseases, Alzheimer's disease and Parkinson's disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases...
October 2, 2018: Scientific Reports
Matthew Neal, Jie Luo, Dilshan S Harischandra, Richard Gordon, Souvarish Sarkar, Huajun Jin, Vellareddy Anantharam, Laurent Désaubry, Anumantha Kanthasamy, Arthi Kanthasamy
Astrocyte reactivity is disease- and stimulus-dependent, adopting either a proinflammatory A1 phenotype or a protective, anti-inflammatory A2 phenotype. Recently, we demonstrated, using cell culture, animal models and human brain samples, that dopaminergic neurons produce and secrete higher levels of the chemokine-like signaling protein Prokineticin-2 (PK2) as a compensatory protective response against neurotoxic stress. As astrocytes express a high level of PK2 receptors, herein, we systematically characterize the role of PK2 in astrocyte structural and functional properties...
October 2018: Glia
Yujeong Lee, Jung-Hyun Cho, Seulah Lee, Wonjong Lee, Seung-Cheol Chang, Hae Young Chung, Hyung Ryong Moon, Jaewon Lee
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are considered promising therapeutic targets in several neurodegenerative diseases. A number of PPAR agonists have been shown to have neuroprotective properties in the presence of oxidative stress, neuroinflammatory response, and apoptosis in various neurodegenerative disease. MHY908 is a novel PPAR α/γ dual agonist, which has been shown to suppress inflammatory response and attenuate insulin resistance in aged rats and db/db mice...
September 28, 2018: Brain Research
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
Sujata Prasad, James R Lokensgard
Activated CD8+ lymphocytes infiltrate the brain in response to many viral infections; where some remain stationed long term as memory T cells. Brain-resident memory T cells (bTRM ) are positioned to impart immediate defense against recurrent or reactivated infection. The cytokine and chemokine milieu present within a tissue is critical for TRM generation and retention; and reciprocal interactions exist between brain-resident glia and bTRM . High concentrations of TGF-β are found within brain and this cytokine has been shown to induce CD103 (integrin αeβ7) expression...
September 18, 2018: Viral Immunology
Craig D Hughes, Minee L Choi, Mina Ryten, Lee Hopkins, Anna Drews, Juan A Botía, Maria Iljina, Magarida Rodrigues, Sarah A Gagliano, Sonia Gandhi, Clare Bryant, David Klenerman
Despite the wealth of genomic and transcriptomic data in Parkinson's disease (PD), the initial molecular events are unknown. Using LD score regression analysis, we show significant enrichment in PD heritability within regulatory sites for LPS-activated monocytes and that TLR4 expression is highest within human substantia nigra, the most affected brain region, suggesting a role for TLR4 inflammatory responses. We then performed extended incubation of cells with physiological concentrations of small alpha-synuclein oligomers observing the development of a TLR4-dependent sensitized inflammatory response with time, including TNF-α production...
September 17, 2018: Acta Neuropathologica
Hwei-Hsien Chen, Pei-Chi Chang, Shiaw-Pyng Wey, Pei-Mei Chen, Chinpiao Chen, Ming-Huan Chan
Parkinson's disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion...
December 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anne Grünewald, Kishore R Kumar, Carolyn M Sue
New discoveries providing insights into mitochondrial bioenergetics, their dynamic interactions as well as their role in cellular homeostasis have dramatically advanced our understanding of the neurodegenerative process of Parkinson's disease (PD). Respiratory chain impairment is a key feature in sporadic PD patients and there is growing evidence that links proteins encoded by PD-associated genes to disturbances in mitochondrial function. Against the backdrop of latest advances in the development of PD treatments that target mitochondria, we aim to give an overview of the literature published in the last three decades on the significance of mitochondria in the pathogenesis of PD...
September 13, 2018: Progress in Neurobiology
Ye Zhao, Shikara Keshiya, Farzaneh Atashrazm, Jianqun Gao, Lars M Ittner, Dario R Alessi, Glenda M Halliday, Yuhong Fu, Nicolas Dzamko
Leucine-rich repeat kinase 2 (LRRK2) is genetically implicated in both familial and sporadic Parkinson's disease (PD). Moreover, LRRK2 has emerged as a compelling therapeutic target for the treatment of PD. Consequently, there is much interest in understanding LRRK2 and its role in PD pathogenesis. LRRK2 is constitutively phosphorylated on two serines, S910 and S935, that are required for interaction of LRRK2 with members of the 14-3-3 family of scaffolding proteins. Pathogenic LRRK2 missense mutations impair the phosphorylation of LRRK2 at these sites, but whether this contributes to PD pathology is unclear...
December 2018: Neurobiology of Disease
Elizabeth B Moloney, Alyssa Moskites, Eliza J Ferrari, Ole Isacson, Penelope J Hallett
GPNMB is a glycoprotein observed upon tissue damage and inflammation and is associated with astrocytes, microglia, and macrophages. Gene variations in GPNMB are linked with Parkinson's disease (PD) risk, and changes in protein levels of GPNMB have been found in lysosomal storage disorders, including Gaucher's disease with glucocerebrosidase (GCase) deficiency. In the current study, GPNMB increases were seen in the substantia nigra (SN) of PD patients compared to age-matched controls. Such PD patients have a decrease in GCase activity and corresponding elevation of glycosphingolipids in the SN (Rocha et al...
August 24, 2018: Neurobiology of Disease
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
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