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Stress AND multiple sclerosis

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https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#1
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28228068/stress-in-gastrointestinal-tract-and-stable-gastric-pentadecapeptide-bpc-157-finally-do-we-have-a-solution
#2
Predrag Sikiric, Sven Seiwerth, Rudolf Rucman, Domagoj Drmic, Mirjana Stupnisek, Antonio Kokot, Marko Sever, Ivan Zoricic, Zoran Zoricic, Lovorka Batelja, Tihomil Ziger, Josipa Vlainic, Zarko Rasic, Martina Lovric Bencic
Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress...
February 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#3
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28204825/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#4
Jing-Xing Zhang, Rui Wang, Jin Xi, Lin Shen, An-You Zhu, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, Feng-Chao Wang, He-Zuo Lü, Jian-Guo Hu
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202372/gut-microbiota-implications-in-parkinson-s-disease
#5
REVIEW
Arun Parashar, Malairaman Udayabanu
Gut microbiota (GM) can influence various neurological outcomes, like cognition, learning, and memory. Commensal GM modulates brain development and behavior and has been implicated in several neurological disorders like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, anxiety, stress and much more. A recent study has shown that Parkinson's disease patients suffer from GM dysbiosis, but whether it is a cause or an effect is yet to be understood. In this review, we try to connect the dots between GM and PD pathology using direct and indirect evidence...
February 7, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28163215/vegf-alleviates-als-csf-induced-cytoplasmic-accumulations-of-tdp-43-and-fus-tls-in-nsc-34-cells
#6
Shubham Shantanu, K Vijayalakshmi, S Shruthi, B K Chandrasekhar Sagar, T N Sathyaprabha, A Nalini, Trichur R Raju, Phalguni Anand Alladi
Cytoplasmic mislocalisation and aggregation of TDP-43 and FUS/TLS proteins in spinal motor neurons contribute to the pathogenesis of the highly fatal disorder amyotrophic lateral sclerosis (ALS). We investigated the neuroprotective effect of VEGF on expression of these proteins in the motor neuronal cell line NSC-34 modelled to reminisce sporadic form of ALS. We studied the expression of TDP-43 and FUS/TLS proteins after exposure to ALS-CSF and following VEGF supplementation by quantitative confocal microscopy and electron microscopy...
February 2, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28152396/insulin-resistance-atherogenicity-and-iron-metabolism-in-multiple-sclerosis-with-and-without-depression-associations-with-inflammatory-and-oxidative-stress-biomarkers-and-uric-acid
#7
Sayonara Rangel Oliveira, Ana Paula Kallaur, Josiane Lopes, Andrea Name Colado Simão, Edna Maria Vissoci Reiche, Elaine Regina Delicato de Almeida, Helena Kaminami Morimoto, Wildea Lice de Carvalho Jennings de Pereira, Daniela Frizon Alfieri, Tamires Flauzino, Caio de Meleck Proença, Anna Maria Gomes, Damacio Ramón Kaimen-Maciel, Michael Maes
Depression is accompanied by metabolic disorders in iron metabolism, lipoproteins, and insulin resistance. We measured plasma levels of ferritin, iron, lipids, insulin, and glucose and computed the homeostasis model assessment (HOMA2IR) and atherogenic index of plasma (AIP) in MS patients with and without depression and healthy controls. Explanatory variables were serum uric acid, interleukin (IL)-6, lipid hydroperoxides (CL-LOOH), albumin, and C-reactive protein (CRP). Depression was assessed using the Hospital Anxiety and Depression Scale (HADS), neurological disability using the Expanded Disability Status Scale (EDSS), and disease progression using ∆EDSS over five years earlier...
December 27, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/28139754/intranasal-delivery-of-a-novel-amnion-cell-secretome-prevents-neuronal-damage-and-preserves-function-in-a-mouse-multiple-sclerosis-model
#8
Reas S Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, Aleta L Svitak, Howard Wessel, Larry Brown, Kenneth S Shindler
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28132855/bone-marrow-derived-mesenchymal-stem-cells-expressing-thioredoxin-1-attenuate-bleomycin-induced-skin-fibrosis-and-oxidative-stress-in-scleroderma
#9
Miao Jiang, Yiwu Yu, Jingying Luo, Qingyun Gao, Lili Zhang, Qiangxiong Wang, Jingjun Zhao
Systemic sclerosis (SSc) is an autoimmune disorder that affects multiple organs. It is characterised by a thickening of the dermis and connective tissue caused by collagen accumulation, and vascular injuries that induce hypoxia. The present study investigated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) expressing thioredoxin 1 (Trx-1) in treating SSc-mediated skin disease following transplantation into a bleomycin-induced murine model. Mice with bleomycin-induced SSc were subcutaneously injected with BMSCs or Trx-1-overexpressing BMSCs and exposed to hypoxic conditions for 48 h...
January 26, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28131782/inhibitory-effects-of-antihistamines-diphenhydramine-and-chlorpheniramine-on-proton-currents-in-bv2-microglial-cells
#10
Jiwon Kim, Jin-Ho Song
Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (HV1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique...
January 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28131195/disease-progression-and-oxidative-stress-are-associated-with-higher-serum-ferritin-levels-in-patients-with-multiple-sclerosis
#11
Katerine Panichi Zanin Ferreira, Sayonara R Oliveira, Ana Paula Kallaur, Damacio R Kaimen-Maciel, Marcell Alysson B Lozovoy, Elaine Regina Delicato de Almeida, Helena Kaminami Morimoto, Leda Mezzaroba, Isaias Dichi, Edna Maria Vissoci Reiche, Andréa Name Colado Simão
Hyperferritinemia and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS). The aim of the present study was to evaluate the serum levels of ferritin and to verify their association with oxidative stress markers and MS progression. This study included 164 MS patients, which were divided in two groups according to their levels of ferritin (cut off 125.6μg/L). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl groups of protein and total radical-trapping antioxidant parameter (TRAP)...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28116039/dimethyl-fumarate-induces-glutathione-recycling-by-upregulation-of-glutathione-reductase
#12
Christina Hoffmann, Michael Dietrich, Ann-Kathrin Herrmann, Teresa Schacht, Philipp Albrecht, Axel Methner
Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate (DMF) is an effective oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. DMF activates the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) leading to increased synthesis of the major cellular antioxidant glutathione (GSH) and prominent neuroprotection in vitro. We previously demonstrated that DMF is capable of raising GSH levels even when glutathione synthesis is inhibited, suggesting enhanced GSH recycling...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28115010/rab32-connects-er-stress-to-mitochondrial-defects-in-multiple-sclerosis
#13
Yohannes Haile, Xiaodan Deng, Carolina Ortiz-Sandoval, Nasser Tahbaz, Aleksandra Janowicz, Jian-Qiang Lu, Bradley J Kerr, Nicholas J Gutowski, Janet E Holley, Paul Eggleton, Fabrizio Giuliani, Thomas Simmen
BACKGROUND: Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between the triggering of the unfolded protein response (UPR) and downstream mitochondrial dysfunction are poorly understood, the membranous contacts between the ER and mitochondria, called the mitochondria-associated membrane (MAM), could provide a functional link between these two mechanisms...
January 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28100077/effects-of-m2000-d-mannuronic-acid-on-learning-memory-retrieval-and-associated-determinants-in-a-rat-model-of-alzheimer-s-disease
#14
Somayeh Athari Nik Azm, Mohammadreza Vafa, Mohammad Sharifzadeh, Majid Safa, Anis Barati, Abbas Mirshafiey
The d-mannuronic acid (M2000) is a novel nonsteroidal anti-inflammatory drug that has immunosuppressive effects together with antioxidant property. M2000 has shown a notable efficacy in experimental models of multiple sclerosis, rheumatoid arthritis, and nephrotic syndrome. In this work, the effect of M2000 on the treatment of Alzheimer's disease (AD) was performed by Morris water maze experiment, and the immunological assessments were carried out by Western blot, apoptosis (procaspase-3, Bax/Bcl2, P53), enzymatic (superoxide dismutase [SOD]), and nonenzymatic oxidative stress (malondialdehyde [MDA]) tests...
February 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#15
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28093706/heat-shock-proteins-in-multiple-sclerosis
#16
Ortan Pinar, Yildirim Akan Ozden, Erkizan Omur, Gedizlioglu Muhtesem
Multiple sclerosis (MS) is an immune-mediated and neurodegenerative central nervous system disease, mostly affect myelin sheaths. The MS pathogenesis is still under debate. It is influenced by genetic, environment factors. Heat shock proteins (HSPs) are highly conserved proteins seen in all organisms. Not only heat stress but also under many stress conditions they are overexpressed. Their roles in MS pathogenesis are highly correlated with their location (intracellular or extracellular). In this chapter, we will discuss the role of HSP in MS pathogenesis...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28093705/manipulation-of-oxygen-and-endoplasmic-reticulum-stress-factors-as-possible-interventions-for-treatment-of-multiple-sclerosis-evidence-for-and-against
#17
Paul Eggleton, Gary R Smerdon, Janet E Holley, Nicholas J Gutowski
Multiple sclerosis (MS) is normally considered a chronic inflammatory disease of the central nervous system (CNS), where T-cells breaching the blood brain barrier react against proteins of the axonal myelin sheaths, leading to focal plaques and demyelination in the brain and spinal cord. Many current therapies are immunosuppressive in nature and are designed to target the immune system at an early stage of the disease. But there is no cure and MS may evolve into a neurodegenerative disease, where immunomodulatory treatments appear less effective...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28086920/absence-of-system-xc-on-immune-cells-invading-the-central-nervous-system-alleviates-experimental-autoimmune-encephalitis
#18
Ellen Merckx, Giulia Albertini, Magdalena Paterka, Cathy Jensen, Philipp Albrecht, Michael Dietrich, Joeri Van Liefferinge, Eduard Bentea, Lise Verbruggen, Thomas Demuyser, Lauren Deneyer, Jan Lewerenz, Geert van Loo, Jacques De Keyser, Hideyo Sato, Pamela Maher, Axel Methner, Ann Massie
BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System xc(-) or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration...
January 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28063173/identification-of-highly-connected-hub-genes-in-the-protective-response-program-of-human-macrophages-and-microglia-activated-by-alpha-b-crystallin
#19
Inge R Holtman, Malika Bsibsi, Wouter H Gerritsen, Hendrikus W G M Boddeke, Bart J L Eggen, Paul van der Valk, Markus Kipp, Johannes M van Noort, Sandra Amor
The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14(+) cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation...
January 7, 2017: Glia
https://www.readbyqxmd.com/read/28049398/infectious-agents-and-neurodegenerative-diseases-exploring-the-links
#20
Mohammad Zubair Alam, Qamre Alam, Mohammad Amjad Kamal, Asif Ahmad Jiman-Fatani, Esam I Azhar, Mohammad Azhar Khan, Absarul Haque
Recent studies have shown that bacterial and viral infections are risk factors for various neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), Alzheimer's disease (AD), and Lyme disease (LD). However, it is still controversial how the infections play a role in neurological diseases progression. Infections in central nervous system may lead multiple damages in infected and neighboring cells. The infection leads to the activation of inflammatory processes and host immune responses, which acts as defense mechanism and also causes damage to the host neuronal functions and viability...
January 3, 2017: Current Topics in Medicinal Chemistry
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