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Drug induced neurodegeneration

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https://www.readbyqxmd.com/read/28939237/brief-isoflurane-administration-as-a-post-exposure-treatment-for-organophosphate-poisoning
#1
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 5minutes after intoxication...
September 19, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#2
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
#3
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
#4
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
#5
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
#6
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...
August 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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28738379/neurodegeneration-neuroregeneration-and-neuroprotection-in-psychiatric-disorders
#10
Siu W Tang, Daiga M Helmeste, Brian E Leonard
Prevention of deterioration of brain function over time is important in the long-term management of chronic brain disorders such as dementia, schizophrenia, and mood disorders. Although the possibility of neurogenesis in the adult human brain is attractive, and there are psychiatric drugs proven to be effective inducers of neurogenesis in animals, we have yet to see their utility in clinical practice. The terms neurodegeneration and neuroregeneration are often used in a nonspecific manner. Neuroregeneration may mean neurogenesis, dendritogenesis, spinogenesis, or axonogenesis...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28736294/enhanced-neuroprotection-of-anthocyanin-loaded-peg-gold-nanoparticles-against-a%C3%AE-1-42-induced-neuroinflammation-and-neurodegeneration-via-the-nf-kb-jnk-gsk3%C3%AE-signaling-pathway
#11
Min Ju Kim, Shafiq Ur Rehman, Faiz Ul Amin, Myeong Ok Kim
Amyloid-beta (Aβ1-42) plaques and neurofibrillary tangles (NFTs) are the main hallmarks considered to be associated with neuroinflammation in Alzheimer's disease (AD). Recently, nanoparticle-based targeted drug delivery approaches have been found to be a useful tool in the neurotherapeutics field. Therefore, we examined and compared the neuroprotective effect of anthocyanins alone and anthocyanin-loaded poly (ethylene glycol)-gold nanoparticles (PEG-AuNPs) in Aβ1-42-injected mouse and in vitro models of AD...
July 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28713238/targeting-cognitive-impairment-in-multiple-sclerosis-the-road-toward-an-imaging-based-biomarker
#12
Jeroen Van Schependom, Guy Nagels
Multiple Sclerosis (MS) is a neuro-degenerative and -inflammatory disease leading to physical and cognitive impairment, pathological fatigue and depression, and affecting patients' quality of life and employment status. The combination of inflammation, demyelination, and neurodegeneration leads to the emergence of MS lesions, reduced white and gray matter brain volumes, a reduced conduction velocity and microstructural changes in the so-called Normal Appearing White Matter (NAWM). Currently, there are very limited options to treat cognitive impairment and its origin is only poorly understood...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28699721/comparison-of-pre-and-post-ischemic-treatment-of-telmisartan-and-nimodipine-combination-in-experimentally-induced-cerebral-ischemia
#13
(no author information available yet)
Time dependent intervention plays a crucial role in preventing neurodegeneration after ischemic insult. The intensity of excitotoxicity is greater in the secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2 h), which could be attributed to secondary elevation of excitatory amino acids (EAA) in cerebral ischemia. In the present study, we tried to assess the neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the secondary reperfusion phase. The drug treatments were made immediately after reperfusion and their effects were compared with pre-treatment...
September 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/28697282/exploring-the-potential-of-natural-and-synthetic-neuroprotective-steroids-against-neurodegenerative-disorders-a-literature-review
#14
REVIEW
Ranju Bansal, Ranjit Singh
Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents...
July 11, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28687315/nadph-oxidase-contributes-to-streptozotocin-induced-neurodegeneration
#15
Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Andrea Rodrigues Vasconcelos, Cristoforo Scavone, Rosana Camarini, Marina S Hernandes, Luiz Roberto Britto
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory. The neurodegeneration induced by AD has been linked to oxidative damage. However, little is known about the involvement of NADPH oxidase 2 (Nox2), a multisubunit enzyme that catalyzes the reduction of oxygen to produce reactive oxygen species, in the pathogenesis of AD. The main purpose of this study was to investigate the involvement of Nox2 in memory, in AD-related brain abnormalities, oxidative damage, inflammation and neuronal death in the hippocampus in the streptozotocin (STZ)-induced AD-like state by comparing the effects of that drug on mice lacking gp91(phox-/-) and wild-type (Wt) mice...
July 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28676261/an-assay-to-detect-dna-damaging-agents-that-induce-nucleotide-excision-repairable-dna-lesions-in-living-human-cells
#16
Reine Takatsuka, Shunsuke Ito, Shigenori Iwai, Isao Kuraoka
Biochemical risk assessment studies of chemicals that induce DNA lesions are important, because lesions in genomic DNA frequently result in cancer, neurodegeneration, and aging in humans. Many classes of DNA lesions induced by chemical agents are eliminated via DNA repair mechanisms, such as nucleotide excision repair (NER) and base excision repair (BER), for the maintenance of genomic integrity. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration...
August 2017: Mutation Research
https://www.readbyqxmd.com/read/28676012/statins-and-the-brain-more-than-lipid-lowering-agents
#17
Anna Fracassi, Martina Marangoni, Pamela Rosso, Valentina Pallottini, Marco Fioramonti, Silvia Siteni, Marco Segatto
BACKGROUND: Statins represent a class of medications widely prescribed to efficiently treat dyslipidemia. These drugs inhibit 3-βhydroxy 3β-methylglutaryl Coenzyme A reductase (HMGR), the rate-limiting enzyme of mevalonate (MVA) pathway. Besides cholesterol, MVA pathway leads to the production of several other compounds, which are essential in the regulation of a plethora of biological activities, including in the central nervous system. For these reasons, statins are able to induce pleiotropic actions, and acquired increased interest as potential and novel modulators in brain processes, especially during pathological conditions...
July 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28666800/a-novel-glp-1-gip-dual-agonist-is-more-effective-than-liraglutide-in-reducing-inflammation-and-enhancing-gdnf-release-in-the-mptp-mouse-model-of-parkinson-s-disease
#18
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28657934/multitarget-botanical-pharmacotherapy-in-major-depression-a-toxic-brain-hypothesis
#19
Siu W Tang, Wayne H Tang, Brain E Leonard
A significant number of patients with major depression do not respond optimally to current antidepressant drugs. As depression is likely to be a heterogeneous disorder, it is possible that existing neurotransmitter-based antidepressant drugs do not fully address other pathologies that may exist in certain cases. Biological pathologies related to depression that have been proposed and studied extensively include inflammation and immunology, hypercortisolemia, oxidative stress, and impaired angiogenesis. Such pathologies may induce neurodegeneration, which in turn causes cognitive impairment, a symptom increasingly being recognized in depression...
June 27, 2017: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28655823/can-an-fda-approved-alzheimer-s-drug-be-repurposed-for-alleviating-neuronal-symptoms-of-zika-virus
#20
Devika Sirohi, Richard J Kuhn
Zika virus caught the world by surprise by its rapid spread and frightening disease outcomes. This major epidemic motivated many scientists to focus their attention on controlling this emerging pathogen. As many as 45 vaccine candidates are being developed, but progress in the antiviral arena has been slower. In a recent article (mBio 8:e00350-17, 2017, https://doi.org/10.1128/mBio.00350-17), Costa and colleagues showed that an FDA-approved drug used to treat Alzheimer's disease may moderate Zika virus-induced neuronal damage...
June 27, 2017: MBio
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