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https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#1
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550248/cd44-splice-variants-as-potential-players-in%C3%A2-alzheimer-s-disease-pathology
#2
Elhanan Pinner, Yaron Gruper, Micha Ben Zimra, Don Kristt, Moshe Laudon, David Naor, Nava Zisapel
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, deposition of amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles, and neuronal cell death. Neuroinflammation is commonly believed to participate in AD pathogenesis. CD44 is an inflammation-related gene encoding a widely-distributed family of alternatively spliced cell surface glycoproteins that have been implicated in inflammation, metastases, and inflammation-linked neuronal injuries. Here we investigated the expression patterns of CD44S (which does not contain any alternative exon) and CD44 splice variants in postmortem hippocampal samples from AD patients and matched non-AD controls...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550168/reduced-expression-of-foxp1-as-a-contributing-factor-in-huntington-s-disease
#3
Anto Sam Crosslee Louis Sam Titus, Tanzeen Yusuff, Marlène Cassar, Elizabeth Thomas, Doris Kretzschmar, Santosh R D'Mello
Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine expansion in the huntington protein (htt). The neuropathological hallmark of HD is the loss of neurons in the striatum and, to a lesser extent, in the cortex. Foxp1 is a member of the Forkhead family of transcription factors expressed selectively in the striatum and the cortex. In the brain, three major Foxp1 isoforms are expressed - isoform-A (∼90 kDa), isoform-D (∼70 kDa) and isoform-C (∼50 kDa). We find that expression of Foxp1 isoforms A and D is selectively reduced in the striatum and cortex of R6/2 HD mice as well as in the striatum of HD patients...
May 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28549843/topical-coenzyme-q10-demonstrates-mitochondrial-mediated-neuroprotection-in-a-rodent-model-of-ocular-hypertension
#4
Benjamin Michael Davis, Kailin Tian, Milena Pahlitzsch, Jonathan Brenton, Nivedita Ravindran, Gibran Butt, Giulia Malaguarnera, Eduardo Normando, Li Guo, Maria Francesca Cordeiro
Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α-tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts...
May 23, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28549492/ginsenoside-rb1-attenuates-isoflurane-surgery-induced-cognitive-dysfunction-via-inhibiting-neuroinflammation-and-oxidative-stress
#5
Hui Hui Miao, Ye Zhang, Guan Nan Ding, Fang Xiao Hong, Peng Dong, Ming Tian
OBJECTIVE: Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress. METHODS: Five-months-old C57BL/6J female mice were treated with 1...
May 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28548834/subtly-modulating-glycogen-synthase-kinase-3-%C3%AE-allosteric-inhibitors-development-and-their-potential-for-the-treatment-of-chronic-diseases
#6
Valle Palomo, Daniel I Pérez, Carlos Roca, Cara Anderson, Natalia Rodriguez-Muela, Concepción Pérez, Jose A Morales-Garcia, Julio A Reyes, Nuria E Campillo, Ana M Pérez-Castillo, Lee L Rubin, Lubov T Timchenko, Carmen Gil, Ana Martínez
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments we are developing small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-activity relationships and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are here presented. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated to strong GSK-3β inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28547794/antidepressant-like-effects-of-tetrahydroxystilbene-glucoside-in-mice-involvement-of-bdnf-signaling-cascade-in-the-hippocampus
#7
Hao Wang, Ying Zhao, Ying-Jie Wang, Lu Song, Jin-Liang Wang, Chao Huang, Wei Zhang, Bo Jiang
BACKGROUND AND AIMS: Current antidepressants in clinic need weeks of administration and always have significant limitations. Tetrahydroxystilbene glucoside (TSG) is one of the major bioactive ingredients of Polygonum multiflorum with neuroprotective effects. This study aimed to evaluate the antidepressant effects of TSG in mice. METHODS: The antidepressant-like effects of TSG in mice were examined in the forced swim test (FST), tail suspension test (TST), and chronic social defeat stress (CSDS) model of depression...
May 25, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28546827/chemical-constituents-from-a-gynostemma-laxum-and-their-antioxidant-and-neuroprotective-activities
#8
Ji Yeon Seo, Sang Kyum Kim, Phi Hung Nguyen, Ju Yong Lee, Pham Ha Thanh Tung, Sang Hyun Sung, Won Keun Oh
BACKGROUND: A few bioactivities of constituents from Gynostemma laxum, which has been collected in Vietnam, have been reported until now. There is no report about the effects of constituents from G. laxum although the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) antioxidant defense system is involved in neuroprotection in the brain. Therefore, we investigated whether quercetin (2), benzoic acid (10) and their analogues (1, 3-9 and 11) from G. laxum have the antioxidant and neuroprotective activities and also their underlying mechanism...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28546552/melatonin-mediated-mitophagy-protects-against-early-brain-injury-after-subarachnoid-hemorrhage-through-inhibition-of-nlrp3-inflammasome-activation
#9
Shenglong Cao, Sudeep Shrestha, Jianru Li, Xiaobo Yu, Jingyin Chen, Feng Yan, Guangyu Ying, Chi Gu, Lin Wang, Gao Chen
The NLRP3 inflammasome is activated in the early period following subarachnoid hemorrhage(SAH), resulting in inflammatory responses. Recent studies have shown that activation of NLRP3 inflammasome is suppressed by autophagy, but the potential mechanism is unclear. In this study, we examined whether mitophagy was involved in the beneficial effect of melatonin and its relationship with NLRP3 inflammasome activation after SAH. In total, 130 adult-male SD rats were randomly divided into four groups: sham group, SAH + vehicle group, SAH + melatonin group, and SAH + 3-methyladenine (3-MA) + melatonin group...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546432/regulation-of-the-endoplasmic-reticulum-stress-response-and-neuroprotective-effects-of-acupuncture-on-brain-injury-caused-by-heroin-addiction
#10
Yong-Long Gao, Yang Zhang, Jiang-Peng Cao, Sheng-Bing Wu, Xing-Hui Cai, Yan-Chun Zhang, Rong-Jun Zhang, Xiao-Ge Song, Li-Da Zhang
OBJECTIVES: To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group...
May 25, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/28545972/lithium-alleviates-neurotoxic-prion-peptide-induced-synaptic-damage-and-neuronal-death-partially-by-the-upregulation-of-nuclear-target-rest-and-the-restoration-of-wnt-signaling
#11
Zhiqi Song, Wei Yang, Xiangmei Zhou, Lifeng Yang, Deming Zhao
Prion diseases are a group of infectious neurodegenerative diseases characterized by multiple neuropathological hallmarks, including accumulation of PrP(Sc), synaptic damage, and neuronal death. We previously reported that the repressor element 1-silencing transcription factor (REST), a novel neuroprotective marker in neurodegeneration, protects neurons against neurotoxic peptide (PrP106-126)-induced neurotoxicity, but fails to maintain survival following prolonged exposure to PrP106-126. Because Wnt signaling partially induces REST and is activated by lithium, we investigated the effects of lithium on REST in prion diseases...
May 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28545897/resveratrol-relieves-angiostrongylus-cantonensis-induced-meningoencephalitis-by-activating-sirtuin-1
#12
An-Chih Chen, Ling-Yuh Shyu, Yue-Loong Hsin, Ke-Min Chen, Shih-Chan Lai
Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice...
May 22, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28545594/early-blockade-of-joint-inflammation-with-a-fatty-acid-amide-hydrolase-inhibitor-decreases-end-stage-osteoarthritis-pain-and-peripheral-neuropathy-in-mice
#13
Jason J McDougall, Milind M Muley, Holly T Philpott, Allison Reid, Eugene Krustev
BACKGROUND: The endocannabinoid system has been shown to reduce inflammatory flares and pain in rodent models of arthritis. A limitation of endocannabinoids is that they are rapidly denatured by hydrolysing enzymes such as fatty acid amide hydrolase (FAAH) which renders them physiologically inert. Osteoarthritis (OA) is primarily a degenerative joint disease; however, it can incorporate mild inflammation and peripheral neuropathy. The aim of this study was to determine whether early blockade of FAAH bioactivity could reduce OA-associated inflammation and joint neuropathy...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28544207/application-of-linear-gradient-elution-in-countercurrent-chromatography-for-the-separation-of-triterpenoid-saponins-from-the-roots-of-pulsatilla-koreana-nakai
#14
Kyoung Jin Lee, Kwangho Song, Da Young Song, Yeong Shik Kim
A linear gradient elution method using countercurrent chromatography was developed for the separation of four triterpenoid saponins from the roots of Pulsatilla koreana Nakai, including hederacolchiside E, which is responsible for the neuroprotective activity of this plant. The target fraction was obtained by 80% methanol elution of solid phase column chromatography. The partition coefficients of the target compounds were very different, which means they are difficult to separate with a single biphasic solvent system...
May 19, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28544038/supplementation-with-herbal-extracts-to-promote-behavioral-and-neuroprotective-effects-in-experimental-models-of-parkinson-s-disease-a-systematic-review
#15
REVIEW
Ianara Mendonça da Costa, José Rodolfo Lopes de Paiva Cavalcanti, Dinalva Brito de Queiroz, Eduardo Pereira de Azevedo, Amália Cinthia Meneses do Rêgo, Irami Araújo Filho, Paulo Parente, Marco Antônio Botelho, Fausto Pierdoná Guzen
Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models...
May 22, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28543594/the-neuroprotective-role-of-mir-124-3p-in-a-6-hydroxydopamine-induced-cell-model-of-parkinson-s-disease-via-the-regulation-of-anax5
#16
Rui-Fang Dong, Bing Zhang, Li-Wen Tai, Hong-Mei Liu, Fang-Kun Shi, Ning-Ning Liu
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Several pathogenetic factors have been involved in the onset and progression of PD, including inflammation, oxidative stress, unfolded protein accumulation, and apoptosis. Ample evidence indicates that miRNAs could regulate post-transcriptional gene expression and neuronal disease. In this study, we evaluated the effects and mechanism of miR-124-3p on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and SH-SY5Y cells...
May 25, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542985/cholinesterase-reactivators-and-bioscavengers-for-pre-and-post-exposure-treatments-of-organophosphorus-poisoning
#17
REVIEW
Patrick Masson, Florian Nachon
Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for post-exposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations...
May 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28542481/effect-of-hyperbaric-oxygen-on-bdnf-release-and-neuroprotection-investigations-with-human-mesenchymal-stem-cells-and-genetically-modified-nih3t3-fibroblasts-as-putative-cell-therapeutics
#18
Jennifer Schulze, Odett Kaiser, Gerrit Paasche, Hans Lamm, Andreas Pich, Andrea Hoffmann, Thomas Lenarz, Athanasia Warnecke
Hyperbaric oxygen therapy (HBOT) is a noninvasive widely applied treatment that increases the oxygen pressure in tissues. In cochlear implant (CI) research, intracochlear application of neurotrophic factors (NTFs) is able to improve survival of spiral ganglion neurons (SGN) after deafness. Cell-based delivery of NTFs such as brain-derived neurotrophic factor (BDNF) may be realized by cell-coating of the surface of the CI electrode. Human mesenchymal stem cells (MSC) secrete a variety of different neurotrophic factors and may be used for the development of a biohybrid electrode in order to release endogenously-derived neuroprotective factors for the protection of residual SGN and for a guided outgrowth of dendrites in the direction of the CI electrode...
2017: PloS One
https://www.readbyqxmd.com/read/28542454/controlled-delivery-of-tauroursodeoxycholic-acid-from-biodegradable-microspheres-slows-retinal-degeneration-and-vision-loss-in-p23h-rats
#19
Laura Fernández-Sánchez, Irene Bravo-Osuna, Pedro Lax, Alicia Arranz-Romera, Victoria Maneu, Sergio Esteban-Pérez, Isabel Pinilla, María Del Mar Puebla-González, Rocío Herrero-Vanrell, Nicolás Cuenca
Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique...
2017: PloS One
https://www.readbyqxmd.com/read/28542400/intracellular-ca2-homeostasis-and-jak1-stat3-pathway-are-involved-in-the-protective-effect-of-propofol-on-bv2-microglia-against-hypoxia-induced-inflammation-and-apoptosis
#20
Yan Lu, Yuechao Gu, Xiaowei Ding, Jiaqiang Wang, Jiawei Chen, Changhong Miao
BACKGROUND: Perioperative hypoxia may induce microglial inflammation and apoptosis, resulting in brain injury. The neuroprotective effect of propofol against hypoxia has been reported, but the underlying mechanisms are far from clear. In this study, we explored whether and how propofol could attenuate microglia BV2 cells from CoCl2-induced hypoxic injury. METHODS: Mouse microglia BV2 cells were pretreated with propofol, and then stimulated with CoCl2. TNF-α level in the culture medium was measured by ELISA kit...
2017: PloS One
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