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Alzheimers mast cell

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https://www.readbyqxmd.com/read/27629855/the-role-of-mast-cells-in-alzheimer-s-disease
#1
REVIEW
Yasdani B Shaik-Dasthagirisaheb, Pio Conti
Immunity and inflammation are deeply involved in Alzheimer's disease. The most important properties of pathological Alzheimer's disease are the extracellular deposits of amyloid â-protein plaque aggregates along with other unknown mutated proteins, which are implicated in immunity and inflammation. Mast cells are found in the brain of all mammalian species and in the periphery, and their biological mediators, including cytokines/chemokines, arachidonic acid products and stored enzymes, play an import role in Alzheimer's disease...
July 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/26702336/the-latest-innovations-in-the-drug-pipeline-for-multiple-sclerosis
#2
Lea Radick, Stanton R Mehr
Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell-targeting monoclonal antibody with a promising new mechanism of action...
November 2015: American Health & Drug Benefits
https://www.readbyqxmd.com/read/26190965/brain-fog-inflammation-and-obesity-key-aspects-of-neuropsychiatric-disorders-improved-by-luteolin
#3
REVIEW
Theoharis C Theoharides, Julia M Stewart, Erifili Hatziagelaki, Gerasimos Kolaitis
Brain "fog" is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain "fog" characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as "minimal cognitive impairment," an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain "fog" may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation...
2015: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/26109673/hemichannels-are-required-for-amyloid-%C3%AE-peptide-induced-degranulation-and-are-activated-in-brain-mast-cells-of-appswe-ps1de9-mice
#4
Paloma A Harcha, Aníbal Vargas, Chenju Yi, Annette A Koulakoff, Christian Giaume, Juan C Sáez
Mast cells (MCs) store an array of proinflammatory mediators in secretory granules that are rapidly released upon activation by diverse conditions including amyloid beta (Aβ) peptides. In the present work, we found a rapid degranulation of cultured MCs through a pannexin1 hemichannel (Panx1 HC)-dependent mechanism induced by Aβ25-35 peptide. Accordingly, Aβ25-35 peptide also increased membrane current and permeability, as well as intracellular Ca(2+) signal, mainly via Panx1 HCs because all of these responses were drastically inhibited by Panx1 HC blockers and absent in the MCs of Panx1(-/-) mice...
June 24, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25982926/altered-expression-of-brain-proteinase-activated-receptor-2-trypsin-2-and-serpin-proteinase-inhibitors-in-parkinson-s-disease
#5
Michael J Hurley, Pascal F Durrenberger, Steve M Gentleman, Andrew F Walls, David T Dexter
Neuroinflammation is thought to contribute to cell death in neurodegenerative disorders, but the factors involved in the inflammatory process are not completely understood. Proteinase-activated receptor-2 (PAR2) expression in brain is increased in Alzheimer's disease and multiple sclerosis, but the status of PAR2 in Parkinson's disease is unknown. This study examined expression of PAR2 and endogenous proteinase activators (trypsin-2, mast cell tryptase) and proteinase inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant to neurodegeneration in Parkinson's disease at different Braak α-synuclein stages of the disease in post-mortem brain...
September 2015: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/25961655/masitinib-for-the-treatment-of-mild-to-moderate-alzheimer-s-disease
#6
REVIEW
Jaume Folch, Dmitry Petrov, Miren Ettcheto, Ignacio Pedrós, Sonia Abad, Carlos Beas-Zarate, Alberto Lazarowski, Miguel Marin, Jordi Olloquequi, Carme Auladell, Antoni Camins
Alzheimer's disease (AD) is a degenerative neurological disorder that is the most common cause of dementia and disability in older patients. Available treatments are symptomatic in nature and are only sufficient to improve the quality of life of AD patients temporarily. A potential strategy, currently under investigation, is to target cell-signaling pathways associated with neurodegeneration, in order to decrease neuroinflammation, excitotoxicity, and to improve cognitive functions. Current review centers on the role of neuroinflammation and the specific contribution of mast cells to AD pathophysiology...
June 2015: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/25714965/new-kid-on-the-block-does-histamine-get-along-with-inflammation-in-amyotrophic-lateral-sclerosis
#7
REVIEW
Cinzia Volonté, Chiara Parisi, Savina Apolloni
Results from amyotrophic lateral sclerosis (ALS) patients and pre-clinical studies strongly suggest that systemic and CNS-intrinsic immune activation plays a central role in ALS pathogenesis. Microglial cells are emerging in this context as master regulators with a bi-functional role in the progression of the pathological response. They foster a pro-inflammatory setting through the production of cytotoxic cytokines and chemokines (M1 phenotype), after an aborted effort to sustain an anti-inflammatory environment for motor neurons through the release of beneficial cytokines and growth factors (M2 phenotype)...
2015: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/25446620/role-of-histaminergic-system-in-blood-brain-barrier-dysfunction-associated-with-neurological-disorders
#8
REVIEW
Ivette Bañuelos-Cabrera, María Guadalupe Valle-Dorado, Blanca Irene Aldana, Sandra Adela Orozco-Suárez, Luisa Rocha
Blood-brain barrier (BBB) disruption has been associated with several acute and chronic brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. This represents a critical situation because damaged integrity of the BBB is related to the influx of immune mediators, plasma proteins and other outside elements from blood to the central nervous system (CNS) that may trigger a cascade of events that leads to neuroinflammation. In this review, evidence that mast cells and the release of factors such as histamine play an important role in the neuroinflammatory process associated with brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy is presented...
November 2014: Archives of Medical Research
https://www.readbyqxmd.com/read/24388213/pathogenic-mechanisms-of-bradykinin-mediated-diseases-dysregulation-of-an-innate-inflammatory-pathway
#9
REVIEW
Allen P Kaplan, Kusumam Joseph
Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor XIIa followed by factor XII fragment (factor XIIf)...
2014: Advances in Immunology
https://www.readbyqxmd.com/read/23810836/slc10a4-what-do-we-know-about-the-function-of-this-secret-ligand-carrier-protein
#10
COMMENT
Karin Borges
This commentary discusses the possible functions of a relatively newly described solute carrier protein, Slc10a4, in regards to a recent article by Zelano et al. (2013) published in the January issue of Experimental Neurology, 239, 73-81. Slc10a4 belongs to the sodium-bile acid cotransporter family (Slc10), but does not show plasma membrane transport activity of bile acids and related molecules. It is co-localized with synaptic vesicle transporters for acetylcholine and dopamine. In Slc10a4 lacking mice, Zelano et al...
October 2013: Experimental Neurology
https://www.readbyqxmd.com/read/23758741/innate-and-adaptive-immune-responses-in-neurodegeneration-and-repair
#11
Sandra Amor, M Nicola Woodroofe
Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders...
March 2014: Immunology
https://www.readbyqxmd.com/read/22632748/molecular-link-mechanisms-between-inflammation-and-cancer
#12
REVIEW
D B Vendramini-Costa, J E Carvalho
Inflammation is part of the body's response to internal and external environmental stimuli that normally eliminate the aggressor agent and restore the tissue physiology. However, when it becomes chronic, it can cause several pathologies such as cardiovascular, diabetes, rheumatoid arthritis, Alzheimer's autoimmune diseases and cancer. Currently, epidemiological data indicate that over 25% of all cancers are related to chronic infections and other types of unresolved inflammation. Further evidence of this relationship is the fact that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk to developing many types of cancers...
2012: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/22562473/mast-cells-an-expanding-pathophysiological-role-from-allergy-to-other-disorders
#13
REVIEW
Preet Anand, Baldev Singh, Amteshwar Singh Jaggi, Nirmal Singh
The mast cells are multi-effector cells with wide distribution in the different body parts and traditionally their role has been well-defined in the development of IgE-mediated hypersensitivity reactions including bronchial asthma. Due to the availability of genetically modified mast cell-deficient mice, the broadened pathophysiological role of mast cells in diverse diseases has been revealed. Mast cells exert different physiological and pathophysiological roles by secreting their granular contents, including vasoactive amines, cytokines and chemokines, and various proteases, including tryptase and chymase...
July 2012: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/21504563/masitinib-as-an-adjunct-therapy-for-mild-to-moderate-alzheimer-s-disease-a-randomised-placebo-controlled-phase-2-trial
#14
François Piette, Joël Belmin, Hélène Vincent, Nicolas Schmidt, Sylvie Pariel, Marc Verny, Caroline Marquis, Jean Mely, Laurence Hugonot-Diener, Jean-Pierre Kinet, Patrice Dubreuil, Alain Moussy, Olivier Hermine
INTRODUCTION: Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated...
2011: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/20858978/csf-levels-of-the-histamine-metabolite-tele-methylhistamine-are-only-slightly-decreased-in-alzheimer-s-disease
#15
COMPARATIVE STUDY
Mouhammad Motawaj, Katell Peoc'h, Jacques Callebert, Jean-Michel Arrang
Neuropathological studies have reported a strong neurofibrillary degeneration of the tuberomamillary nucleus, the region of origin of histamine neurons, in Alzheimer's disease (AD). Histaminergic neurons enhance cognition and memory, suggesting that their degeneration may contribute to the cognitive decline of AD. Besides neurons, the brain histaminergic system comprises mast cells and microglia that can also produce histamine. The level of activity of this histaminergic system in AD remained unknown. In the present study, we have measured the levels of the main histamine metabolite in brain, tele-methylhistamine (t-MeHA), an index of histaminergic system activity, in the cerebrospinal fluid (CSF) of 97 non-AD (controls) and 91 AD patients, males or females...
2010: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/20406178/involvement-of-immune-response-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis-a-therapeutic-opportunity
#16
REVIEW
A Calvo, C Moglia, M Balma, A Chiò
The immune system has been found to be involved with positive and negative effects in the nervous system of amyotrophic lateral sclerosis (ALS) patients. In general, T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage. Several mechanisms of action, such as production of neurotrophic growth factors and interaction with neurons and glial cells, have been shown to preserve these latter from injury and stimulate growth and repair...
July 2010: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/20033190/choroid-plexus-biology-and-pathology
#17
REVIEW
Hartwig Wolburg, Werner Paulus
The choroid plexus is an epithelial-endothelial vascular convolute within the ventricular system of the vertebrate brain. It consists of epithelial cells, fenestrated blood vessels, and the stroma, dependent on various physiological or pathological conditions, which may contain fibroblasts, mast cells, macrophages, granulocytes or other infiltrates, and a rich extracellular matrix. The choroid plexus is mainly involved in the production of cerebrospinal fluid (CSF) by using the free access to the blood compartment of the leaky vessels...
January 2010: Acta Neuropathologica
https://www.readbyqxmd.com/read/19844812/involvement-of-fc-receptors-in-disorders-of-the-central-nervous-system
#18
REVIEW
Eitan Okun, Mark P Mattson, Thiruma V Arumugam
Immunoglobulins are proteins with a highly variable antigen-binding domain and a constant region (Fc domain) that binds to a cell surface receptor (FcR). Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells) triggers effector responses including cytokine production, phagocytosis, and degranulation. In addition to their roles in normal responses to infection or tissue injury, and in immune-related diseases, FcRs are increasingly recognized for their involvement in neurological disorders...
June 2010: Neuromolecular Medicine
https://www.readbyqxmd.com/read/19505377/amyloid-beta-peptides-trigger-cd47-dependent-mast-cell-secretory-and-phagocytic-responses
#19
N Niederhoffer, R Levy, E Sick, P Andre, G Coupin, Y Lombard, J P Gies
Mast cells are found in the brain, where they contribute to immune responses. They have been implicated in multiple sclerosis, but their potential role in Alzheimers disease (AD), another inflammatory disease of the central nervous system, remains elusive. In the present study, we examined mast cell responses to amyloid beta (Abeta) peptides 1-40 and 1-42, the major components of the Alzheimer amyloid plaques. Rat peritoneal mast cells were used as experimental model for human brain serosal mast cells. Fibrillar Abeta1-40 and Ami1-42 peptides induced concentration-dependent exocytosis, as assessed by measurement of histamine secretion; exocytosis was reduced by pre-treatment with pertussis toxin and with antibodies against the CD47 receptor and the beta1-integrin subunit...
April 2009: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/19000712/protective-autoimmunity-in-the-nervous-system
#20
REVIEW
Jerome J Graber, Suhayl Dhib-Jalbut
The immune system can play both detrimental and beneficial roles in the nervous system. Multiple arms of the immune system, including T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage to the nervous system during toxic, ischemic, hemorrhagic, infective, degenerative, metabolic and immune-mediated insults and also assist in the process of repair after injury has occurred. Immune cells have been shown to produce neurotrophic growth factors and interact with neurons and glial cells to preserve them from injury and stimulate growth and repair...
February 2009: Pharmacology & Therapeutics
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