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Stress model for neurodegenerative disorders

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https://www.readbyqxmd.com/read/28642233/sembragiline-a-novel-selective-monoamine-oxidase-type-b-inhibitor-for-the-treatment-of-alzheimer-s-disease
#1
Edilio Borroni, Bernd Bohrmann, Fiona Grueninger, Eric Prinssen, Stephane Nave, Hansruedi Loetscher, Shankar J Chinta, Subramanian Rajagopalan, Anand Rane, Almas Siddiqui, Bart Ellenbroek, Juerg Messer, Axel Pahler, Julie K Anderson, Rene Wyler, Andrea M Cesura
Monoamine oxidase B (MAO-B) has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased MAO-B expression in astroglia has been observed adjacent to amyloid plaques in AD patient brains. This phenomenon is hypothesised to lead to increased production of hydrogen peroxide and reactive oxygen species (ROS), thereby contributing to AD pathology. Therefore, reduction of ROS-induced oxidative stress via inhibition of MAO-B activity may delay the progression of the disease...
June 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28641540/metallothionein-is-a-potential-therapeutic-strategy-for-amyotrophic-lateral-sclerosis
#2
Shin-Ichi Ono
Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 mice, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human mutant SOD1s...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640972/understanding-adaptogenic-activity-specificity-of-the-pharmacological-action-of-adaptogens-and-other-phytochemicals
#3
REVIEW
Alexander Panossian
Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28611658/neuroprotective-and-anti-aging-potentials-of-essential-oils-from-aromatic-and-medicinal-plants
#4
REVIEW
Muhammad Ayaz, Abdul Sadiq, Muhammad Junaid, Farhat Ullah, Fazal Subhan, Jawad Ahmed
The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28592637/in-vivo-imaging-of-prodromal-hippocampus-ca1-subfield-oxidative-stress-in-models-of-alzheimer-disease-and-angelman-syndrome
#5
Bruce A Berkowitz, Jacob Lenning, Nikita Khetarpal, Catherine Tran, Johnny Y Wu, Ali M Berri, Kristin Dernay, E Mark Haacke, Fatema Shafie-Khorassani, Robert H Podolsky, John C Gant, Shaniya Maimaiti, Olivier Thibault, Geoffrey G Murphy, Brian M Bennett, Robin Roberts
Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/T1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI...
June 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28588483/plastic-and-neuroprotective-mechanisms-involved-in-the-therapeutic-effects-of-cannabidiol-in-psychiatric-disorders
#6
REVIEW
Alline C Campos, Manoela V Fogaça, Franciele F Scarante, Sâmia R L Joca, Amanda J Sales, Felipe V Gomes, Andreza B Sonego, Naielly S Rodrigues, Ismael Galve-Roperh, Francisco S Guimarães
Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28577963/physiological-and-pathological-processes-of-synaptic-plasticity-and-memory-in-drug-discovery-do-not-forget-the-dose-response-curve
#7
Jos Prickaerts, Nick P Van Goethem, Walter Gulisano, Elentina K Argyrousi, Agostino Palmeri, Daniela Puzzo
The response of a biological system to an endogenous or exogenous molecule depends upon the dose. For this reason, performing dose-response curves is crucial to understand physiological and pathophysiological phenomena, and to predict the effect of a drug. Most of the studies in pharmacological research have been performed according to the classical threshold model, focusing on higher doses able to ensure a biological effect. However, recent evidences pointed out the need to investigate the effect of low doses...
May 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28575743/igf-ii-promotes-neuroprotection-and-neuroplasticity-recovery-in-a-long-lasting-model-of-oxidative-damage-induced-by-glucocorticoids
#8
E Martín-Montañez, C Millon, F Boraldi, F Garcia-Guirado, C Pedraza, E Lara, L J Santin, J Pavia, M Garcia-Fernandez
Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT)...
May 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28571715/the-novel-multitarget-iron-chelating-and-propargylamine-drug-m30-affects-app-regulation-and-processing-activities-in-alzheimer-s-disease-models
#9
REVIEW
Tamar Amit, Orit Bar-Am, Danit Mechlovich, Lana Kupershmidt, Moussa B H Youdim, Orly Weinreb
In many of the neurodegenerative diseases, such as Alzheimer's disease (AD) and AD-related disorders, as well as in the regular ageing process, excessive generation of oxidative stress (OS) and accumulation of iron levels and deposition have been observed in specific affected-brain regions and thus, regarded as contributing factors to the pathogenesis of the diseases. In AD, iron promotes amyloid β (Aβ) neurotoxicity by producing free radical damage and OS in brain areas affected by neurodegeneration, presumably by facilitating the aggregation of Aβ...
May 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#10
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
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
#11
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/28542430/ros-regulation-of-axonal-mitochondrial-transport-is-mediated-by-ca2-and-jnk-in-drosophila
#12
Pin-Chao Liao, Lauren C Tandarich, Peter J Hollenbeck
Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two...
2017: PloS One
https://www.readbyqxmd.com/read/28479719/caffeic-acid-phenethyl-ester-cape-prevents-development-of-stz-icv-induced-dementia-in-rats
#13
Manish Kumar, Devinder Kaur, Nitin Bansal
BACKGROUND: Chronic oxidative stress and inflammation severely affect the normal physiology of neurons and lead to neurodegenerative disorders such as Alzheimer's disease (AD). Polyphenols proved a boon in the prevention of dementia due to their antioxidant and neuroprotective potential. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound attributed with antioxidant, immunomodulatory, and neuroprotective properties. OBJECTIVE: The present study investigates the effect of CAPE on experimental dementia in rats...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28479214/the-protective-effect-of-astaxanthin-on-learning-and-memory-deficits-and-oxidative-stress-in-a-mouse-model-of-repeated-cerebral-ischemia-reperfusion
#14
Yan Xue, Zhenzhen Qu, Jian Fu, Junli Zhen, Wenjing Wang, Yunlei Cai, Weiping Wang
Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorders, such as vascular cognitive impairment (VCI). The present study was performed to investigate the potential neuroprotective effect of the antioxidant astaxanthin (ATX) in a mouse model of VCI. VCI was induced in male ICR mice by repeated occlusion of the bilateral common carotid artery, leading to repeated cerebral ischemia/reperfusion (IR) injury. After surgery, the mice received ATX or an equal volume of vehicle by daily intragastric administration for 28days...
May 4, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28478802/electroacupuncture-ameliorates-spatial-learning-and-memory-impairment-via-attenuating-nox2-related-oxidative-stress-in-a-rat-model-of-alzheimer-s-disease-induced-by-a%C3%AE-1-42
#15
G Wu, L Li, H-M Li, Y Zeng, W-C Wu
Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognition and memory, in which oxidative stress has been played a crucial role in the pathology of AD. Electroacupuncture (EA) is a widely used therapy based on traditional acupuncture combined with modern electrotherapy in Asia. The present study aimed to determine the effects of EA treatment on spatial learning and memory impairment, and to elucidate the status of NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Beta-amyloid1-42 (Aβ1-42)...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28474205/chaperone-co-inducer-bgp-15-inhibits-histone-deacetylases-and-enhances-the-heat-shock-response-through-increased-chromatin-accessibility
#16
Marek A Budzyński, Tim Crul, Samu V Himanen, Noemi Toth, Ferenc Otvos, Lea Sistonen, Laszlo Vigh
Defects in cellular protein homeostasis are associated with many severe and prevalent pathological conditions such as neurodegenerative diseases, muscle dystrophies, and metabolic disorders. One way to counteract these defects is to improve the protein homeostasis capacity through induction of the heat shock response. Despite numerous attempts to develop strategies for chemical activation of the heat shock response by heat shock transcription factor 1 (HSF1), the underlying mechanisms of drug candidates' mode of action are poorly understood...
May 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28458159/celastrol-reduces-il-1%C3%AE-induced-matrix-catabolism-oxidative-stress-and-inflammation-in-human-nucleus-pulposus-cells-and-attenuates-rat-intervertebral-disc-degeneration-in-vivo
#17
Jian Chen, Jun Xuan, Yun-Tao Gu, Ke-Si Shi, Jun-Jun Xie, Jiao-Xiang Chen, Zeng-Ming Zheng, Yu Chen, Xi-Bang Chen, Yao-Sen Wu, Xiao-Lei Zhang, Xiang-Yang Wang
Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1β treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1β in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB pathway was inhibited by celastrol in nucleus pulposus cells...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28455141/identification-of-potential-therapeutic-compounds-for-parkinson-s-disease-using-drosophila-and-human-cell-models
#18
Francisco José Sanz, Cristina Solana-Manrique, Verónica Muñoz-Soriano, Pablo Calap-Quintana, María Dolores Moltó, Nuria Paricio
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5-10% of them are familial forms caused by mutations in certain genes...
April 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28450128/protective-effects-of-lichen-metabolites-evernic-and-usnic-acids-against-redox-impairment-mediated-cytotoxicity-in-central-nervous-system-like-cells
#19
Carlos Fernández-Moriano, Pradeep Kumar Divakar, Ana Crespo, M Pilar Gómez-Serranillos
Lichens species produce unique secondary metabolites that attract increasing pharmacological interest, including their redox modulatory activities. Current work evaluated for the first time the in vitro cytoprotective properties, based on the antioxidant activities, of the Parmeliaceae lichens Evernia prunastri and Usnea ghattensis and the mechanism of action of their major phenolic constituents: the evernic and usnic acids, respectively. In two models of central nervous system-like cells (U373-MG and SH-SY5Y cell lines), exogenous H2O2 induced oxidative stress-mediated cytotoxicity...
April 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28427412/lack-of-interleukin-13-receptor-%C3%AE-1-delays-the-loss-of-dopaminergic-neurons-during-chronic-stress
#20
Simone Mori, Shuei Sugama, William Nguyen, Tatiana Michel, M Germana Sanna, Manuel Sanchez-Alavez, Rigo Cintron-Colon, Gianluca Moroncini, Yoshihiko Kakinuma, Pamela Maher, Bruno Conti
BACKGROUND: The majority of Parkinson's disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress...
April 21, 2017: Journal of Neuroinflammation
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