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Drug induced neurodegeneration

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https://www.readbyqxmd.com/read/28643372/fine-tuning-perk-signaling-for-neuroprotection
#1
REVIEW
Mark Halliday, Daniel Hughes, Giovanna Mallucci
Protein translation and folding are tightly controlled processes in all cells, by proteostasis, an important component of which is the unfolded protein response (UPR). During periods of endoplasmic reticulum stress due to protein misfolding, the UPR activates a coordinated response in which the PERK branch activation restricts translation, while a variety of genes involved with protein folding, degradation, chaperone expression and stress responses are induced through signaling of the other branches. Chronic overactivation of the UPR, particularly the PERK branch is observed in the brains of patients in a number of protein misfolding neurodegenerative diseases, including Alzheimer's, and Parkinson's diseases and the taopathies...
June 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28643232/caffeine-protects-against-anticonvulsant-induced-neurotoxicity-in-the-developing-rat-brain
#2
Stefanie Endesfelder, Ulrike Weichelt, Cornelia Schiller, Marco Sifringer, Ivo Bendix, Christoph Bührer
Phenobarbital is the most commonly used drug for the treatment of neonatal seizures but may induce neurodegeneration in the developing brain. Methylxanthine caffeine is used for the treatment of apnea in newborn infants and appears to be neuroprotective, as shown by antiapoptotic and anti-inflammatory effects in oxidative stress models in newborn rodents and reduced rates of cerebral palsy in human infants treated with caffeine. We hypothesized that caffeine may counteract the proapoptotic effects of phenobarbital in newborn rats...
June 22, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28641491/nicotine-and-cigarette-smoke-modulate-nrf2-bdnf-dopaminergic-signal-and-neurobehavioral-disorders-in-adult-rat-cerebral-cortex
#3
Nibedita Naha, D N Gandhi, A K Gautam, J Ravi Prakash
BACKGROUND: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28624183/the-neuroprotective-effect-of-perampanel-in-lithium-pilocarpine-rat-seizure-model
#4
Ting Wu, Katsutoshi Ido, Yoshihide Osada, Sadaharu Kotani, Akira Tamaoka, Takahisa Hanada
PURPOSE: Status epilepticus (SE) causes irreversible neurodegeneration if not terminated quickly. Perampanel (PER), a potent AMPA receptor antagonist, has previously been shown to terminate seizures in the lithium-pilocarpine SE model. In the present study, we assessed whether PER would also prevent neuronal damage in this model. METHODS: SE was induced in rats using lithium chloride and pilocarpine. Initiation of SE was defined as continuous seizures that exhibited as rearing accompanied by bilateral forelimb clonus (Racine score 4)...
June 14, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28588483/plastic-and-neuroprotective-mechanisms-involved-in-the-therapeutic-effects-of-cannabidiol-in-psychiatric-disorders
#5
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/28578514/the-beneficial-effects-of-hmg-coa-reductase-inhibitors-in-the-processes-of-neurodegeneration
#6
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Alireza Arefidoust, Ahmad Reza Dehpour
Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties...
June 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28577132/tangeretin-inhibits-neurodegeneration-and-attenuates-inflammatory-responses-and-behavioural-deficits-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-induced-parkinson-s-disease-dementia-in-rats
#7
Jin-Song Yang, Xiao-Hong Wu, Hao-Gang Yu, Li-Song Teng
Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests...
June 2, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28575866/catalpol-protects-synaptic-proteins-from-beta-amyloid-induced-neuron-injury-and-improves-cognitive-functions-in-aged-rats
#8
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...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28567016/streptomyces-sp-mum212-as-a-source-of-antioxidants-with-radical-scavenging-and-metal-chelating-properties
#9
Loh Teng-Hern Tan, Kok-Gan Chan, Tahir Mehmood Khan, Sarah Ibrahim Bukhari, Surasak Saokaew, Acharaporn Duangjai, Priyia Pusparajah, Learn-Han Lee, Bey-Hing Goh
Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28539529/membrane-trafficking-illuminates-a-path-to-parkinson-s-disease
#10
Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki
Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28528366/cdk5-mediated-phosphorylation-dependent-ubiquitination-and-degradation-of-e3-ubiquitin-ligases-gp78-accelerates-neuronal-death-in-parkinson-s-disease
#11
Qingzhi Wang, Fengjuan Jiao, Pei Zhang, Jianguo Yan, Zheng Zhang, Feng He, Qian Zhang, Zexi Lv, Xiang Peng, Hongwei Cai, Bo Tian
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD...
May 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#12
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28515689/current-experimental-studies-of-gene-therapy-in-parkinson-s-disease
#13
REVIEW
Jing-Ya Lin, Cheng-Long Xie, Su-Fang Zhang, Weien Yuan, Zhen-Guo Liu
Parkinson's disease (PD) was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28507726/adapting-tissue-engineered-in-vitro-cns-models-for-high-throughput-study-of-neurodegeneration
#14
Caitriona O'Rourke, Charlotte Lee-Reeves, Rosemary Al Drake, Grant Ww Cameron, A Jane Loughlin, James B Phillips
Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28504195/fgf18-protects-against-6-hydroxydopamine-induced-nigrostriatal-damage-in-a-rat-model-of-parkinson-s-disease
#15
Xingzhi Guo, Tingting Liu, Diandian Zhao, Xiaofeng Wang, Dongmei Liu, Yang He, Chang Shan, Yingying Kong, Weiwei Hu, Bei Tao, Lihao Sun, Hongyan Zhao, Shengtian Li, Jianmin Liu
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway...
May 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28487766/malathion-increases-apoptotic-cell-death-by-inducing-lysosomal-membrane-permeabilization-in-n2a-neuroblastoma-cells-a-model-for-neurodegeneration-in-alzheimer-s-disease
#16
Ramu Venkatesan, Yong Un Park, Eunhee Ji, Eui-Ju Yeo, Sun Yeou Kim
Malathion is an organophosphate with severe neurotoxic effects. Upon acute exposure, malathion initially enhances cholinergic activity by inhibition of acetylcholinesterase, which is its major pathological mechanism. Malathion also induces non-cholinergic neuronal cell death in neurodegenerative conditions; the associated molecular mechanism is not well-characterized. To investigate the molecular mechanism of malathion-induced cell death, N2a mouse neuroblastoma cells were exposed to malathion and cell death-related parameters were examined...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28479141/neurodegenerative-effects-of-azithromycin-in-differentiated-pc12-cells
#17
Vicki Waetzig, Jeanette Riffert, Justus Cordt, Kirstin Reinecke, Wiebke Haeusgen, Ruwen Boehm, Ingolf Cascorbi, Thomas Herdegen
Azithromycin is a widely used macrolide antibiotic with sustained and high tissue penetration and intracellular accumulation. While short-term exposure to low-dose azithromycin is usually well tolerated, prolonged treatment can lead to unwanted neurological effects like paresthesia and hearing loss. However, the mechanism causing neurodegeneration is still unknown. Here, we show that even low therapeutically relevant azithromycin concentrations like 1µg/ml decreased cell viability by 15% and induced neurite loss of 47% after 96h in differentiated PC12 cells, which are a well-established model system for neuronal cells...
May 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28470518/ferroptosis-and-cell-death-analysis-by-flow-cytometry
#18
Daishi Chen, Ilker Y Eyupoglu, Nicolai Savaskan
Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28442607/n-methyl-d-aspartate-nmda-receptor-blockade-prevents-neuronal-death-induced-by-zika-virus-infection
#19
Vivian V Costa, Juliana L Del Sarto, Rebeca F Rocha, Flavia R Silva, Juliana G Doria, Isabella G Olmo, Rafael E Marques, Celso M Queiroz-Junior, Giselle Foureaux, Julia Maria S Araújo, Allysson Cramer, Ana Luíza C V Real, Lucas S Ribeiro, Silvia I Sardi, Anderson J Ferreira, Fabiana S Machado, Antônio C de Oliveira, Antônio L Teixeira, Helder I Nakaya, Danielle G Souza, Fabiola M Ribeiro, Mauro M Teixeira
Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442167/tipping-points-and-endogenous-determinants-of-nigrostriatal-degeneration-by-mptp
#20
REVIEW
Stefan Schildknecht, Donato A Di Monte, Regina Pape, Kim Tieu, Marcel Leist
The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a Parkinson's disease (PD)-like syndrome by inducing degeneration of nigrostriatal dopaminergic neurons. Studies of the MPTP model have revealed the pathomechanisms underlying dopaminergic neurodegeneration and facilitated the development of drug treatments for PD. In this review, we provide an update on MPTP bioactivation and biodistribution, reconcile the distinct views on energetic failure versus reactive oxygen species (ROS) formation as main drivers of MPTP-induced neurodegeneration, and describe recently identified intrinsic features of the nigrostriatal system that make it particularly vulnerable to MPTP...
April 23, 2017: Trends in Pharmacological Sciences
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