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https://www.readbyqxmd.com/read/30342839/triggers-facilitators-and-aggravators-redefining-parkinson-s-disease-pathogenesis
#1
REVIEW
Michaela E Johnson, Viviane Labrie, Lena Brundin, Patrik Brundin
We hypothesize that Parkinson's disease (PD) pathogenesis can be divided into three temporal phases. During the first phase, 'triggers', such as viral infections or environmental toxins, spark the disease process in the brain and/or peripheral tissues. Triggers alone, however, may be insufficient, requiring 'facilitators' like peripheral inflammation for PD pathology to develop. Once the disease manifests, 'aggravators' spur further neurodegeneration and exacerbate symptoms. Aggravators are proposed to include impaired autophagy and cell-to-cell propagation of α-synuclein pathology...
October 17, 2018: Trends in Neurosciences
https://www.readbyqxmd.com/read/30333787/a-systematic-review-and-meta-analysis-of-alpha-synuclein-auto-antibodies-in-parkinson-s-disease
#2
Kirsten M Scott, Antonina Kouli, Su L Yeoh, Menna R Clatworthy, Caroline H Williams-Gray
Immune dysfunction has been associated with Parkinson's disease (PD) and its progression. Antibodies play an important role in both innate and adaptive responses, acting as powerful effector molecules that can propagate inflammation by activating innate immune cells. Alpha synuclein binding antibodies have been described in PD patients with conflicting associations. In this article, we consider the potential mechanistic basis of alpha synuclein auto-antibody development and function in PD. We present a systematic review and meta-analysis of antibody studies in PD cohorts showing that there is weak evidence for an increase in alpha synuclein auto-antibodies in PD patients particularly in early disease...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/30333729/role-of-microglia-tlrs-in-neurodegeneration
#3
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
https://www.readbyqxmd.com/read/30328585/low-grade-inflammation-aggravates-rotenone-neurotoxicity-and-disrupts-circadian-clock-gene-expression-in-rats
#4
Huan Li, Sheng Song, Yuan Wang, Chun Huang, Feng Zhang, Jie Liu, Jau-Shyong Hong
A single injection of LPS produced low-grade neuroinflammation leading to Parkinson's disease (PD) in mice several months later. Whether such a phenomenon occurs in rats and whether such low-grade neuroinflammation would aggravate rotenone (ROT) neurotoxicity and disrupts circadian clock gene/protein expressions were examined in this study. Male rats were given two injections of LPS (2.5-7.5 mg/kg), and neuroinflammation and dopamine neuron loss were evident 3 months later. Seven months after a single LPS (5 mg/kg) injection, rats received low doses of ROT (0...
October 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/30314597/molecular-imaging-of-the-cholinergic-system-in-parkinson-s-disease
#5
Nicolaas I Bohnen, Prabesh Kanel, Martijn L T M Müller
One of the first identified neurotransmitters in the brain, acetylcholine, is an important modulator that drives changes in neuronal and glial activity. For more than two decades, the main focus of molecular imaging of the cholinergic system in Parkinson's disease (PD) has been on cognitive changes. Imaging studies have confirmed that degeneration of the cholinergic system is a major determinant of dementia in PD. Within the last decade, the focus is expanding to studying cholinergic correlates of mobility impairments, dyskinesias, olfaction, sleep, visual hallucinations and risk taking behavior in this disorder...
2018: International Review of Neurobiology
https://www.readbyqxmd.com/read/30311182/auricular-vagus-nerve-stimulation-exerts-antiinflammatory-effects-and-immune-regulatory-function-in-a-6-ohda-model-of-parkinson-s-disease
#6
Ying Jiang, Zhentang Cao, Huizi Ma, Guihong Wang, Xuemei Wang, Zhan Wang, Yaqin Yang, Huiqing Zhao, Genliang Liu, Longling Li, Tao Feng
According to epidemiologic studies, smoking appears to downregulate the prevalence of Parkinson's disease (PD), possibly due to antiinflammatory mechanisms via activation of α7 nicotinic acetylcholine receptors (α7 nAChRs). This receptor also appears to play a role in T-cell differentiation. Recently, it has become apparent that the innate immune system participates in PD pathogenesis. The aim of this study was to evaluate the effects of auricular vagus nerve stimulation (aVNS) on substantia nigra (SN) dopaminergic neurodegeneration and the associated neuroinflammation and immune responses in a rat PD model...
November 2018: Neurochemical Research
https://www.readbyqxmd.com/read/30306855/peripheral-immunity-immunoaging-and-neuroinflammation-in-parkinson-s-disease
#7
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
https://www.readbyqxmd.com/read/30302409/aldosterone-exerts-anti-inflammatory-effects-on-lps-stimulated-microglia
#8
Björn-Ole Bast, Uta Rickert, Janna Schneppenheim, François Cossais, Henrik Wilms, Philipp Arnold, Ralph Lucius
Over the last years, studies on microglia cell function in chronic neuro-inflammation and neuronal necrosis pointed towards an eminent role of these cells in Multiple Sclerosis, Parkinson's and Alzheimer's Disease. It was found, that microglia cell activity can be stimulated towards a pro- or an anti-inflammatory profile, depending on the stimulating signals. Therefore, investigation of receptors expressed by microglia cells and ligands influencing their activation state is of eminent interest. A receptor found to be expressed by microglia cells is the mineralocorticoid receptor...
October 2018: Heliyon
https://www.readbyqxmd.com/read/30298527/from-nose-to-gut-the-role-of-the-microbiome-in-neurological-disease
#9
Jack S Bell, Jonathan I Spencer, Richard L Yates, Sydney A Yee, Benjamin M Jacobs, Gabriele C DeLuca
Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung, and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS)...
October 8, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/30298049/hiv-1-associated-neurocognitive-disorders-is-hla-c-binding-stability-to-%C3%AE-2-microglobulin-a-missing-piece-of-the-pathogenetic-puzzle
#10
Donato Zipeto, Michela Serena, Simona Mutascio, Francesca Parolini, Erica Diani, Elisabetta Guizzardi, Valentina Muraro, Emanuela Lattuada, Sebastiano Rizzardo, Marina Malena, Massimiliano Lanzafame, Giovanni Malerba, Maria Grazia Romanelli, Stefano Tamburin, Davide Gibellini
AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND) are complications of HIV-1 infection. Viral infections are risk factors for the development of neurodegenerative disorders. Aging is associated with low-grade inflammation in the brain, i.e., the inflammaging. The molecular mechanisms linking immunosenescence, inflammaging and the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are largely unknown. ADC and HAND share some pathological features with AD and may offer some hints on the relationship between viral infections, neuroinflammation, and neurodegeneration...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/30295793/nlrp3-inflammasome-related-proteins-are-upregulated-in-the-putamen-of-patients-with-multiple-system-atrophy
#11
Fangzhou Li, Takashi Ayaki, Takakuni Maki, Nobukatsu Sawamoto, Ryosuke Takahashi
Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia, and autonomic dysfunction. Microglial infiltration is an important mediator in MSA. The nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) inflammasome complex, comprising NLRP3, apoptotic speck protein containing a caspase recruitment domain (ASC), and cysteine aspartic acid protease 1 (Caspase 1), regulates microglial inflammation in several neurodegenerative diseases...
November 1, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/30292735/a-punch-in-the-gut-intestinal-inflammation-links-environmental-factors-to-neurodegeneration-in-parkinson-s-disease
#12
Anouck Becker, Klaus Faßbender, Wolfgang H Oertel, Marcus M Unger
Parkinson's disease (PD) is an etiologically heterogeneous disorder. Experimental, clinical and epidemiological data suggest that intestinal inflammation contributes to the pathogenesis of PD. This article reviews recent literature on gut microbiota and intestinal inflammation in PD. We propose that intestinal inflammation links environmental factors (e.g. an altered gut microbiota composition) to neurodegeneration in (genetically susceptible) PD patients. In addition, there is an epidemiological and genetic overlap between PD and inflammatory bowel disease...
September 29, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/30286516/outcome-of-cell-suspension-allografts-in-a-patient-with-huntington-s-disease
#13
Alexander Maxan, Sarah Mason, Martine Saint-Pierre, Emma Smith, Aileen Ho, Tim Harrower, Colin Watts, Yen Tai, Nicola Pavese, Julie C Savage, Marie-Ève Tremblay, Peter Gould, Anne E Rosser, Stephen B Dunnett, Paola Piccini, Roger A Barker, Francesca Cicchetti
For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here we present the first clinico-pathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multi-centre clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as a major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area...
October 4, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/30283455/cerebrospinal-fluid-inflammatory-cytokine-aberrations-in-alzheimer-s-disease-parkinson-s-disease-and-amyotrophic-lateral-sclerosis-a-systematic-review-and-meta-analysis
#14
Xi Chen, Yang Hu, Zongze Cao, Qingshan Liu, Yong Cheng
It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30276531/frozen-shoulder-or-shoulder-stiffness-from-parkinson-disease
#15
REVIEW
R Papalia, G Torre, G Papalia, M H Baums, P Narbona, V Di Lazzaro, V Denaro
PURPOSE: To understand the role of camptocormia (increased kyphosis) and postural alteration in Parkinson's disease in the development of shoulder pathology, with a special concern for adhesive capsulitis and shoulder stiffness. METHODS: A preliminary online search was carried out, with combination of keywords including "Parkinson," "Shoulder stiffness," "Frozen shoulder," "Adhesive capsulitis," "Postural alteration," "Camptocormia"...
October 1, 2018: Musculoskeletal Surgery
https://www.readbyqxmd.com/read/30258764/3d-tissue-engineering-an-emerging-technique-for-pharmaceutical-research
#16
REVIEW
Gregory Jensen, Christian Morrill, Yu Huang
Tissue engineering and the tissue engineering model have shown promise in improving methods of drug delivery, drug action, and drug discovery in pharmaceutical research for the attenuation of the central nervous system inflammatory response. Such inflammation contributes to the lack of regenerative ability of neural cells, as well as the temporary and permanent loss of function associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. This review is focused specifically on the recent advances in the tissue engineering model made by altering scaffold biophysical and biochemical properties for use in the treatment of neurodegenerative diseases...
September 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30258234/microglia-in-neurodegeneration
#17
REVIEW
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
https://www.readbyqxmd.com/read/30244177/raf-kinase-inhibitor-protein-protects-microglial-cells-against-1-methyl-4-phenylpyridinium-induced-neuroinflammation-in-vitro
#18
Yuanlin Gao, Jie Zhong, Lei Jiang
The Raf kinase inhibitor protein (RKIP), belonging to a member of the phosphatidylethanolamine-binding protein (PEBP) family, is involved in regulating neural development. However, the role of RKIP in microglial cells stimulated with 1-methyl-4-phenylpyridinium (MPP+ ) has not been determined. Thus, in the present study, we investigated the role of RKIP and its underlying mechanism in Parkinson's disease (PD). Our results showed that the expression of RKIP was significantly reduced in BV-2 cells treated with MPP+ ...
September 20, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/30230979/ginger-and-6-shogaol-protect-intestinal-tight-junction-and-enteric-dopaminergic-neurons-against-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-in-mice
#19
Eugene Huh, Jin Gyu Choi, Dongjin Noh, Hyung-Seok Yoo, Jeewon Ryu, Nam-Jung Kim, Hocheol Kim, Myung Sook Oh
OBJECTIVE: Ginger and its compound, 6-shogaol, have been known for improving gastrointestinal (GI) function and reducing inflammatory responses in GI tract. Recently, the treatment of GI dysfunction has been recognized as an important part of the management of neurodegenerative diseases, especially for Parkinson's disease (PD). In this study, we investigated whether ginger and 6-shogaol attenuate disruptions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the intestinal barrier and the enteric dopaminergic neurons...
September 19, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/30222521/immunology-of-west-nile-virus-infection-and-the-role-of-alpha-synuclein-as-a-viral-restriction-factor
#20
Kelsey E Lesteberg, John David Beckham
West Nile virus (WNV) is a single-stranded RNA flavivirus and is a major cause of viral encephalitis worldwide. Experimental models of WNV infection in mice are commonly used to define acute neuroinflammatory responses in the brain. Alpha-synuclein (Asyn) is a protein of primarily neuronal origin and is a major cause of Parkinson's disease (PD), a disorder characterized by loss of dopaminergic neurons. Both WNV and PD pathologies are largely mediated by inflammation of the central nervous system (neuroinflammation) and have overlapping inflammatory pathways...
September 15, 2018: Viral Immunology
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