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Drug induced neurodegeneration

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https://www.readbyqxmd.com/read/29128393/rem-sleep-deprivation-and-dopaminergic-d2-receptors-modulation-increase-recognition-memory-in-an-animal-model-of-parkinson-s-disease
#1
Adriano D S Targa, Ana Carolina D Noseda, Lais S Rodrigues, Mariana F Aurich, Marcelo M S Lima
Cognitive impairment is an important non-motor symptom of Parkinson's disease (PD). The neuronal death in nigrostriatal pathway is the main factor for motor symptoms and recent studies indicate a possible influence in non-motor symptoms as well. The pedunculopontine tegmental nucleus (PPT) and basal ganglia are closely related anatomically and functionally and, since they are affected by neurodegeneration in PD, they might be involved in recognition memory. To investigate this, we promoted an ibotenic acid lesion within the PPT or a rotenone lesion within substantia nigra pars compacta (SNpc) of Wistar rats, followed by 24h of REM sleep deprivation (REMSD)...
November 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29125494/cognitive-enhancing-and-antioxidant-effects-of-tetrahydroxystilbene-glucoside-in-a%C3%AE-1-42-induced-neurodegeneration-in-mice
#2
Miao Xie, Geng Zhang, Wei Yin, Xin-Xin Hei, Tao Liu
Polyhydroxy stilbenes have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease (AD). Tetrahydroxystilbene glucoside is one of the major polyhydroxy stilbenes, which provides underlying therapeutic activities for neuroprotective actions in various experimental conditions. This study intends to investigate the impact of tetrahydroxystilbene glucoside remedy for cognitive disorder and oxidative stress in Aβ1-42-induced AD mice and to clarify the mechanisms of action through Keap1/Nrf2 pathway...
November 7, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/29121589/pharmacological-targeting-of-gsk-3-and-nrf2-provides-neuroprotection-in-a-preclinical-model-of-tauopathy
#3
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29107957/febuxostat-ameliorates-secondary-progressive-experimental-autoimmune-encephalomyelitis-by-restoring-mitochondrial-energy-production-in-a-got2-dependent-manner
#4
Josephe A Honorat, Yuji Nakatsuji, Mikito Shimizu, Makoto Kinoshita, Hisae Sumi-Akamaru, Tsutomu Sasaki, Kazushiro Takata, Toru Koda, Akiko Namba, Kazuya Yamashita, Eri Sanda, Manabu Sakaguchi, Atsushi Kumanogoh, Takashi Shirakura, Mizuho Tamura, Saburo Sakoda, Hideki Mochizuki, Tatsusada Okuno
Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE. A DNA microarray analysis revealed that febuxostat treatment increased the CNS expression of several mitochondria-related genes in EAE mice, most notably including GOT2, which encodes glutamate oxaloacetate transaminase 2 (GOT2)...
2017: PloS One
https://www.readbyqxmd.com/read/29103051/c-abl-and-parkinson-s-disease-mechanisms-and-therapeutic-potential
#5
Saurav Brahmachari, Senthilkumar S Karuppagounder, Preston Ge, Saebom Lee, Valina L Dawson, Ted M Dawson, Han Seok Ko
 Although the etiology of Parkinson's disease (PD) is poorly understood, oxidative stress has long been implicated in the pathogenesis of the disease. However, multifaceted and divergent signaling cascades downstream of oxidative stress have posed challenges for researchers to identify a central component of the oxidative stress-induced pathways causing neurodegeneration in PD. Since 2010, c-Abl-a non-receptor tyrosine kinase and an indicator of oxidative stress-has shown remarkable potential as a future promising drug target in PD therapeutics...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29079998/role-of-3-acetyl-11-keto-beta-boswellic-acid-in-counteracting-lps-induced-neuroinflammation-via-modulation-of-mirna-155
#6
Aya Shoukry Sayed, Iman Emam Omar Gomaa, Michael Bader, Nesrine Salah El Dine El Sayed
Neuroinflammation is one of the most important mechanisms underlying neurodegeneration. Lipopolysaccharide (LPS) is a potent inflammogen which causes cognitive dysfunction. Boswellia serrata is known since many years as a powerful anti-inflammatory herbal drug. Its beneficial effect mainly arises from inhibition of 5-lipoxygenase (5-LO) enzyme. 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent 5-LO inhibitor extracted from the oleo-gum-resin of Boswellia serrata. The aim of the present work is to study the molecular mechanisms underlying the anti-inflammatory and neuroprotective effects of AKBA and dexamethasone (DEX) in LPS-induced neuroinflammatory model...
October 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29072584/impaired-sleep-circadian-rhythms-and-neurogenesis-in-diet-induced-premature-aging
#7
Alexander J Stankiewicz, Erin M McGowan, Lili Yu, Irina V Zhdanova
Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior...
October 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29056550/piperine-in-combination-with-quercetin-halt-6-ohda-induced-neurodegeneration-in-experimental-rats-biochemical-and-neurochemical-evidences
#8
Shamsher Singh, Puneet Kumar
Parkinson's disease (PD) is a multifactorial neurological disorder caused by selective dopaminergic neuronal loss. Quercetin (QC) in combination with piperine (bioenhancer) acts as potential antioxidant, anti-inflammatory and neuroprotective against 6-OHDA rat model of PD. Rats were injected 6-OHDA (8μg/2μl, saline) unilaterally, intranigrally once into right SNpc. Pre-treatment with QC (25 and 50mg/kg, p.o.) alone and combination of QC (25mg/kg, p.o.) with piperine (2.5mg/kg, p.o.) were given for 14days starting from 8th day of 6-OHDA infusion...
October 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29050205/catalpol-protects-synaptic-proteins-from-beta-amyloid-induced-neuron-injury-and-improves-cognitive-functions-in-aged-rats
#9
Zhiming Xia, Fengfei Wang, Shuang Zhou, Rui Zhang, Fushun Wang, Jason H Huang, Erxi Wu, Yongfang Zhang, Yaer Hu
Synapse loss is one of the common factors contributing to cognitive disorders, such as Alzheimer's disease (AD), which is manifested by the impairment of basic cognitive functions including memory processing, perception, problem solving, and language. The current therapies for patients with cognitive disorders are mainly palliative; thus, regimens preventing and/or delaying dementia progression are urgently needed. In this study, we evaluated the effects of catalpol, isolated from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in aged rat models...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28989083/resveratrol-activation-of-ampk-dependent-pathways-is-neuroprotective-in-human-neural-stem-cells-against-amyloid-beta-induced-inflammation-and-oxidative-stress
#10
Ming-Chang Chiang, Christopher J Nicol, Yi-Chuan Cheng
Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss resulting in dementia. Amyloid-beta (Aβ) peptides play a critical role in the pathogenesis of this disease, and are thought to promote inflammation and oxidative stress leading to neurodegeneration in the neocortex and hippocampus of the AD brains. AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis, and cell survival in response to inflammation and oxidative stress. However, the neuroprotective mechanisms by which AMPK achieves these beneficial effects in human neural stem cells (hNSCs) exposed to Aβ is still not well understood...
October 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28945963/the-analgesic-acetaminophen-and-the-antipsychotic-clozapine-can-each-redox-cycle-with-melanin
#11
Zülfikar Temoçin, Eunkyoung Kim, Jinyang Li, Lucia Panzella, Maria Laura Alfieri, Alessandra Napolitano, Deanna L Kelly, William E Bentley, Gregory F Payne
Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context...
October 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28939237/brief-isoflurane-administration-as-a-post-exposure-treatment-for-organophosphate-poisoning
#12
Jishnu K S Krishnan, Taíza H Figueiredo, John R Moffett, Peethambaran Arun, Abhilash P Appu, Narayanan Puthillathu, Maria F Braga, Thomas Flagg, Aryan M Namboodiri
Organophosphate chemical threat agents (OP-CTA) exert toxic effects through cholinergic over-activation. However, after the initial cholinergic phase, the pathophysiology shifts to a non-cholinergic phase which leads to prolonged status epilepticus (SE), irreversible neuronal degeneration and long-term damage to the central nervous system. The efficacy of delayed treatments against OP-CTA is generally low due to the fact that most drugs fail to inhibit the later phase of non-cholinergic activation. Recently, we reported that intranasal brain delivery of obidoxime (OBD) provides complete neuroprotection against a lethal dose of paraoxon when administered 5min after intoxication...
September 20, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#13
Qian Zhang, Mengbi Yang, Kasper K Sørensen, Charlotte S Madsen, Josephine T Boesen, Ying An, Shao Hong Peng, Yuming Wei, Qianwen Wang, Knud J Jensen, Zhong Zuo, Ho Yin Edwin Chan, Jacky Chi Ki Ngo
Polyglutamine (PolyQ) diseases are progressive neurodegenerative disorders caused by both protein- and RNA-mediated toxicities. We previously showed that a peptidyl inhibitor, P3, which binds directly to expanded CAG RNA can inhibit RNA-induced nucleolar stress and suppress RNA-induced neurotoxicity. Here we report a N-acetylated and C-amidated derivative of P3, P3V8, that showed a more than 20-fold increase in its affinity for expanded CAG RNA. The P3V8 peptide also more potently alleviated expanded RNA-induced cytotoxicity in vitro, and suppressed polyQ neurodegeneration in Drosophila with no observed toxic effects...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904242/the-g-quadruplex-dna-stabilizing-drug-pyridostatin-promotes-dna-damage-and-downregulates-transcription-of-brca1-in-neurons
#14
Jose F Moruno-Manchon, Edward C Koellhoffer, Jayakrishnan Gopakumar, Shashank Hambarde, Nayun Kim, Louise D McCullough, Andrey S Tsvetkov
The G-quadruplex is a non-canonical DNA secondary structure formed by four DNA strands containing multiple runs of guanines. G-quadruplexes play important roles in DNA recombination, replication, telomere maintenance, and regulation of transcription. Small molecules that stabilize the G-quadruplexes alter gene expression in cancer cells. Here, we hypothesized that the G-quadruplexes regulate transcription in neurons. We discovered that pyridostatin, a small molecule that specifically stabilizes G-quadruplex DNA complexes, induced neurotoxicity and promoted the formation of DNA double-strand breaks (DSBs) in cultured neurons...
September 12, 2017: Aging
https://www.readbyqxmd.com/read/28880029/fluorescence-labelling-of-extracellular-vesicles-using-a-novel-thiol-based-strategy-for-quantitative-analysis-of-cellular-delivery-and-intracellular-traffic
#15
H D Roberts-Dalton, A Cocks, J M Falcon-Perez, E J Sayers, J P Webber, P Watson, A Clayton, A T Jones
Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neurodegeneration. They are also under intense investigation as delivery vectors for biotherapeutics. The ways in which EVs interact with recipient cells to influence cell physiology and deliver a macromolecular payload are at the early stages of exploration...
September 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28871125/hiv-1-matrix-protein-p17-misfolding-forms-toxic-amyloidogenic-assemblies-that-induce-neurocognitive-disorders
#16
Yasmin Zeinolabediny, Francesca Caccuri, Laura Colombo, Federica Morelli, Margherita Romeo, Alessandro Rossi, Silvia Schiarea, Carlotta Ciaramelli, Cristina Airoldi, Ria Weston, Liu Donghui, Jerzy Krupinski, Rubén Corpas, Elisa García-Lara, Sara Sarroca, Coral Sanfeliu, Mark Slevin, Arnaldo Caruso, Mario Salmona, Luisa Diomede
Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821394/activation-of-ampk-is-neuroprotective-in-the-oxidative-stress-by-advanced-glycosylation-end-products-in-human-neural-stem-cells
#17
Chien-Hung Lin, Yi-Chuan Cheng, Christopher J Nicol, Kuan-Hung Lin, Chia-Hui Yen, Ming-Chang Chiang
Advanced glycosylation end products (AGEs) formation is correlated with the pathogenesis of diabetic neuronal damage, but its links with oxidative stress are still not well understood. Metformin, one of the most widely used anti-diabetic drugs, exerts its effects in part by activation of AMP-activated protein kinase (AMPK). Once activated, AMPK regulates many pathways central to metabolism and energy balance including, glucose uptake, glycolysis and fatty acid oxidation. AMPK is also present in neurons, but its role remains unclear...
October 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28820437/are-astrocytes-the-predominant-cell-type-for-activation-of-nrf2-in-aging-and-neurodegeneration
#18
REVIEW
Jeffrey R Liddell
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes...
August 18, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28811775/metformin-attenuate-ptz-induced-apoptotic-neurodegeneration-in-human-cortical-neuronal-cells
#19
Fehmida Bibi, Ikram Ullah, Myeong Ok Kim, Muhammad Imran Naseer
OBJECTIVE: Seizures are one of the neurodegenerative disorders of human being. Metformin has antioxidant properties and commonly used as an oral antidiabetic drug. The current study was aimed to observe the neuroprotective effect of metformin against PTZ-induced apoptotic neurodegeneration in human cortical neuronal cell culture. METHODS: To observe that exposure of pentylenetetrazol (PTZ) at the dose of (30mM) for 30 minutes induced neuronal cell death by activation of caspase-3 in human cortical neuronal 2 (HCN-2) cell line...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28782388/nanotechnology-based-drug-delivery-of-ropinirole-for-parkinson-s-disease
#20
Emilia Barcia, Liudmila Boeva, Luis García-García, Karla Slowing, Ana Fernández-Carballido, Yaquelyn Casanova, Sofía Negro
A new drug delivery system is developed for ropinirole (RP) for the treatment of Parkinson's disease (PD) consisting of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The formulation selected was prepared with 8 mg RP and 50 mg PLGA 502. This formulation exhibited mean encapsulation efficiency of 74.8 ± 8.2%, mean particle size lower than 155 nm, the zeta potential of -14.25 ± 0.43 mV and zero-order in vitro release of RP (14.13 ± 0.17 μg/h/10 mg NPs) for 5 d...
November 2017: Drug Delivery
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