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inflammation Parkinson

Michael Sommerauer, Norbert Galldiks, Michael T Barbe, Gabriele Stoffels, Antje Willuweit, Heinz H Coenen, Michael Schroeter, Lars Timmermann, Gereon R Fink, Karl-Josef Langen
OBJECTIVES: This study aimed to investigate whether the amino acid PET tracer cis-4-[F]fluoro-D-proline [D-cis-[F]FPro] shows increased uptake in the basal ganglia of patients with neurodegenerative akinetic-rigid parkinsonism. D-Cis-[F]FPro is a sensitive PET tracer for inflammation-associated neurodegeneration in animal models. We hypothesized that D-cis-[F]FPro might also be a sensitive marker of alterations of the basal ganglia in parkinsonian syndromes. PARTICIPANTS AND METHODS: Ten patients with neurodegenerative akinetic-rigid parkinsonism (five with idiopathic Parkinson's disease and five with atypical parkinsonian syndromes) were imaged with D-cis-[F]FPro and compared with 13 patients with brain tumors who had no basal ganglia involvement...
April 2019: Nuclear Medicine Communications
Wenyan Zou, Tinglin Pu, Weixi Feng, Ming Lu, Ying Zheng, Renhong Du, Ming Xiao, Gang Hu
Background: Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis of Parkinson's disease (PD), thus, it is reliable to promote the clearance of α-synuclein to prevent and treat PD. Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules, however, their pathophysiological aspects remain elusive. Method: Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes...
2019: Translational Neurodegeneration
Edwin Jabbari, John Woodside, Tong Guo, Nadia K Magdalinou, Viorica Chelban, Dilan Athauda, Andrew J Lees, Thomas Foltynie, Henry Houlden, Alistair Church, Michele Tm Hu, James B Rowe, Henrik Zetterberg, Huw R Morris
OBJECTIVE: The high degree of clinical overlap between atypical parkinsonian syndromes (APS) and Parkinson's disease (PD) makes diagnosis challenging. We aimed to identify novel diagnostic protein biomarkers of APS using multiplex proximity extension assay (PEA) testing. METHODS: Cerebrospinal fluid (CSF) samples from two independent cohorts, each consisting of APS and PD cases, and controls, were analysed for neurofilament light chain (NF-L) and Olink Neurology and Inflammation PEA biomarker panels...
March 13, 2019: Journal of Neurology, Neurosurgery, and Psychiatry
Stéphanie Pain, Sylvie Bodard, Zuhal Gulhan, Jackie Vergote, Sylvie Chalon, Afsaneh Gaillard
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Interestingly, it has already been shown that an intracerebral administration of neuropeptide Y (NPY) decreases the neurodegeneration induced by 6-hydroxydopamine (6-OHDA) in rodents and prevents loss of dopamine (DA) and DA transporter density. The etiology of idiopathic PD now suggest that chronic production of inflammatory mediators by activated microglial cells mediates the majority of DA-neuronal tissue destruction...
March 13, 2019: Fundamental & Clinical Pharmacology
Francesca Garretti, Dritan Agalliu, Cecilia S Lindestam Arlehamn, Alessandro Sette, David Sulzer
Evidence from a variety of studies implicates a role for the adaptive immune system in Parkinson's disease (PD). Similar to multiple sclerosis (MS) patients who display a high number of T cells in the brain attacking oligodendrocytes, PD patients show higher numbers of T cells in the ventral midbrain than healthy, age-matched controls. Mouse models of the disease also show the presence of T cells in the brain. The role of these infiltrating T cells in the propagation of disease is controversial; however, recent studies indicate that they may be autoreactive in nature, recognizing disease-altered self-proteins as foreign antigens...
2019: Frontiers in Immunology
Xin Fang, Puyuan Tian, Xiaoxiao Zhao, Chunling Jiang, Tingtao Chen
While glucagon-like peptide-1 (GLP-1) was reported to have a positive impact on Parkinson disease, its extremely short half-life greatly hindered its clinical use. In the present study, the mouse strain MG1363-pMG36e-GLP-1 was engineered to continuously express GLP-1 to treat Parkinson disease in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated Parkinson disease model. In our study, oral supplementation with MG1363-pMG36e-GLP-1 significantly (p < 0.05) reduced MPTP-induced locomotor impairments, increased tyrosine hydroxylase (T-OH)-positive neurons, suppressed microglia and astrocyte activation and downregulated expression of several inflammation-related molecules...
March 9, 2019: Journal of Neurochemistry
Brian Spencer, Ivy Trinh, Edward Rockenstein, Michael Mante, Jazmin Florio, Anthony Adame, Omar M A El-Agnaf, Changyoun Kim, Eliezer Masliah, Robert A Rissman
Neurodegenerative disorders of the aging population are characterized by progressive accumulation of neuronal proteins such as α-synuclein (α-syn) in Parkinson's Disease (PD) and Amyloid ß (Aß) and Tau in Alzheimer's disease (AD) for which no treatments are currently available. The ability to regulate the expression at the gene transcription level would be beneficial for reducing the accumulation of these proteins or regulating expression levels of other genes in the CNS. Short interfering RNA molecules can bind specifically to target RNAs and deliver them for degradation...
March 5, 2019: Neurobiology of Disease
Jacek Staszewski, Ewa Skrobowska, Renata Piusińska-Macoch, Bogdan Brodacki, Adam Stępień
PURPOSE: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up. PATIENTS AND METHODS: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited...
March 4, 2019: Advances in Medical Sciences
Namkwon Kim, Cindy Cruz Martínez, Dae Sik Jang, Jong Kil Lee, Myung Sook Oh
Abnormal inflammatory response in the central nervous system plays a critical role in various neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease. Therefore, modulation of abnormal neuroinflammation is thought to be a promising therapeutic strategy for these diseases. Based on this idea, we focused on finding a potential candidate material that would regulate excessive neuroinflammation. Iresine celosia has long been used as a traditional Mexican medicine to treat fever and oral disorders...
March 2019: Biomedicine & Pharmacotherapy
Elisa Caggiu, Giannina Arru, Sepideh Hosseini, Magdalena Niegowska, GianPietro Sechi, Ignazio Roberto Zarbo, Leonardo A Sechi
Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra pars compacta with a reduction of dopamine concentration in the striatum. The complex interaction between genetic and environmental factors seems to play a role in determining susceptibility to PD and may explain the heterogeneity observed in clinical presentations. The exact etiology is not yet clear, but different possible causes have been identified. Inflammation has been increasingly studied as part of the pathophysiology of neurodegenerative diseases, corroborating the hypothesis that the immune system may be the nexus between environmental and genetic factors, and the abnormal immune function can lead to disease...
2019: Frontiers in Neurology
Jillian H Kluss, Adamantios Mamais, Mark R Cookson
The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but variable penetrance and genome-wide association studies have found variants of the gene that are risk factors for sporadic PD. Functional studies have suggested that the common mechanism that links all disease-associated variants is that they increase LRRK2 kinase activity, albeit in different ways...
March 5, 2019: Biochemical Society Transactions
Zuobo Wang, Lin Sun, Kaixue Jia, Hongxia Wang, Xiuxiang Wang
Parkinson's disease (PD) is a most common progressive neurodegenerative disease mainly occurring in the elderly. Plenty of miRNAs are reported to involve in the progression of PD. However, the role of miR-9-5p in the regulation of PD pathogenesis remains unclear. The expressions of miR-9-5p and Sirtuin 1 (SIRT1) at mRNA and protein levels were determined by qRT-PCR and western blotting (WB) analyses. Cell viability and apoptosis were evaluated by MTT and flow cytometry. The levels of apoptosis-related proteins Bcl-2, Bax, Caspase-3 were detected by WB analysis...
February 28, 2019: Neuroscience Letters
Zhi-Lan Zhou, Xue-Bing Jia, Meng-Fei Sun, Ying-Li Zhu, Chen-Meng Qiao, Bo-Ping Zhang, Li-Ping Zhao, Qin Yang, Chun Cui, Xue Chen, Yan-Qin Shen
Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection...
February 27, 2019: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Sara Redenšek, Dušan Flisar, Maja Kojović, Milica Gregorič Kramberger, Dejan Georgiev, Zvezdan Pirtošek, Maja Trošt, Vita Dolžan
BACKGROUND: Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment...
February 27, 2019: Journal of Neuroinflammation
Govindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Sudhanshu P Raikwar, Ramasamy Thangavel, Duraisamy Kempuraj, Iuliia Dubova, Daniyal Saeed, Haris Zahoor, Keerthivaas Premkumar, Smita Zaheer, Shankar Iyer, Asgar Zaheer
Microglial cells are brain specific professional phagocytic immune cells that play a crucial role in the inflammation- mediated neurodegeneration especially in Parkinson's disease (PD) and Alzheimer's disease. Glia maturation factor (GMF) is a neuroinflammatory protein abundantly expressed in the brain. We have previously shown that GMF expression is significantly upregulated in the substantia nigra (SN) of PD brains. However, its possible role in PD progression is still not fully understood. The Clustered-Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR Associated (Cas) protein9 (CRISPR/Cas9) system is a simple, rapid and often extremely efficient gene editing tool at desired loci, enabling complete gene knockout or homology directed repair...
February 27, 2019: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Darius Widera, Rocío Martínez Aguilar, Graeme S Cottrell
Toll-like receptor 4 (TLR4) and protease-activated receptor 2 (PAR2) play pivotal roles in the mammalian innate immune response. Notably, in addition to their involvement in detection of invading pathogens, PAR2 and TLR4 modulate the levels of cell death-induced sterile inflammation by activating pro- or anti-inflammatory downstream signaling cascades. Within the central nervous system, there is emerging evidence that both receptors are involved in synaptic transmission and brain plasticity. Furthermore, due to their prominent role in mediating neuroinflammation, PAR2 and TLR4 are associated with development and progression of neurodegenerative disorders including but not limited to Alzheimer's disease, Parkinson's disease and multiple sclerosis...
July 2019: Neural Regeneration Research
Walther Haenseler, Lawrence Rajendran
Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allow modelling of neurodegeneration in vitro...
February 22, 2019: Stem Cells
Ana-Luisa Gil-Martínez, Cristina Estrada, Lorena Cuenca, Juan-Antonio Cano, Manuel Valiente, Carlos-Manuel Martínez-Cáceres, Emiliano Fernández-Villalba, María-Trinidad Herrero
The cause of progressive degeneration in Parkinson's disease is not clear, although, in the last years, different studies have suggested that both brain and peripheral inflammation could play a key role in the progression of this disorder. In our study, we aimed to analyze the effect of an acute inflammation confined to the colon on dopaminergic neuronal death and glial response in mice intoxicated with MPTP. The results obtained show a very significant decrease of dopaminergic neurons in the SNpc as well as a significant decrease of dopaminergic fibers in the striatum of the MPTP+DSS-treated group compared with the control animals...
February 22, 2019: Neurotoxicity Research
Dmitri Lodygin, Moritz Hermann, Nils Schweingruber, Cassandra Flügel-Koch, Takashi Watanabe, Corinna Schlosser, Arianna Merlini, Henrike Körner, Hsin-Fang Chang, Henrike J Fischer, Holger M Reichardt, Marta Zagrebelsky, Brit Mollenhauer, Sebastian Kügler, Dirk Fitzner, Jens Frahm, Christine Stadelmann, Michael Haberl, Francesca Odoardi, Alexander Flügel
The grey matter is a central target of pathological processes in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. The grey matter is often also affected in multiple sclerosis, an autoimmune disease of the central nervous system. The mechanisms that underlie grey matter inflammation and degeneration in multiple sclerosis are not well understood. Here we show that, in Lewis rats, T cells directed against the neuronal protein β-synuclein specifically invade the grey matter and that this is accompanied by the presentation of multifaceted clinical disease...
February 20, 2019: Nature
Nitya Beriwal, Tashi Namgyal, Pema Sangay, Asmaa Monther Al Quraan
The anti-oxidant effects of melatonin and the immune-pineal axis are well established. However, how they play a role in the pathogenesis of neurodegenerative diseases is not well elucidated. A better understanding of this neuro-immuno-endocrinological link can help in the development of novel therapies with higher efficacy to alleviate symptomatology, slow disease progression and improve the quality of life. Recent studies have shown that the immune-pineal axis acts as an immunological buffer, neurohormonal switch and it also intricately links the pathogenesis of neurodegenerative diseases (like Multiple sclerosis, Alzheimer's disease, Parkinson's disease) and inflammation at a molecular level...
January 2019: Heliyon
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