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Drug induced neurodegeneration

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https://www.readbyqxmd.com/read/29746089/physiological-a%C3%AE-concentrations-produce-a-more-biomimetic-representation-of-the-alzheimer-s-disease-phenotype-in-ipsc-derived-human-neurons
#1
Bonnie J Berry, Alec S T Smith, Christopher J Long, Candace C Martin, James J Hickman
Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at non-physiological concentrations to induce an exaggerated dysfunctional phenotype...
May 10, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29740323/the-selective-antagonism-of-adenosine-a-2b-receptors-reduces-the-synaptic-failure-and-neuronal-death-induced-by-oxygen-and-glucose-deprivation-in-rat-ca1-hippocampus-in-vitro
#2
Irene Fusco, Filippo Ugolini, Daniele Lana, Elisabetta Coppi, Ilaria Dettori, Lisa Gaviano, Daniele Nosi, Federica Cherchi, Felicita Pedata, Maria G Giovannini, Anna M Pugliese
Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1 , A2A , A2B , and A3 . Although adenosine exerts clear neuroprotective effects through A1 receptors during ischemia, the use of selective A1 receptor agonists is hampered by their undesirable peripheral side effects...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29736957/functional-up-regulation-of-the-m-current-by-retigabine-contrasts-hyperexcitability-and-excitotoxicity-on-rat-hypoglossal-motoneurons
#3
Filippo Ghezzi, Laura Monni, Andrea Nistri
KEY POINT SUMMARY: Excessive neuronal excitability characterizes several neuropathological conditions including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Hypoglossal motoneurons (HMs) that control tongue muscles, are extremely vulnerable to this disease and undergo damage and death when exposed to excessive glutamate extracellular concentration that causes excitotoxicity. Our laboratory devised an in vitro model of excitotoxicity obtained by pharmacological block of glutamate transporters...
May 7, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29714132/mir-7-replacement-therapy-in-parkinson-s-disease
#4
Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
The present review examines whether the microRNA 7 (miR-7) holds potential for slowing Parkinson's disease (PD) progression. First, the accurate expression of miR-7 allows for the normal development, physiology, and neurogenesis in the central nervous system, also keeping alpha-synuclein (α-Syn) at the physiological level. Second, patients with PD and parkinsonian MPTP-induced animals exhibit a significant decrease of miR-7 in brain areas associated with dopaminergic neurodegeneration. Depletion of miR-7 in the substantia nigra of clinical samples was related to α-Syn accumulation, loss of dopaminergic cells, and reduction of dopamine in the striatum...
April 30, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29710724/moringa-oleifera-alleviates-homocysteine-induced-alzheimer-s-disease-like-pathology-and-cognitive-impairments
#5
Yacoubou Abdoul Razak Mahaman, Fang Huang, Mengjuan Wu, Yuman Wang, Zhen Wei, Jian Bao, Maibouge Tanko Mahamane Salissou, Dan Ke, Qun Wang, Rong Liu, Jian-Zhi Wang, Bin Zhang, Dan Chen, Xiaochuan Wang
Alzheimer's disease (AD) is multifactorial with unclear etiopathology. Due to the complexity of AD, many attempted single therapy treatments, like Aβ immunization, have generally failed. Therefore, there is a need for drugs with multiple benefits. Naturally occurring phytochemicals with neuroprotective, anti-amyloidogenic, antioxidative, and anti-inflammatory properties could be a possible way out. In this study, the effect of Moringa oleifera (MO), a naturally occurring plant with high antioxidative, anti-inflammatory, and neuroprotective effects, was evaluated on hyperhomocysteinemia (HHcy) induced AD-like pathology in rats...
April 28, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29684590/a-synthetic-snake-venom-based-tripeptide-glu-val-trp-protects-pc12-cells-from-mpp-toxicity-by-activating-the-ngf-signaling-pathway
#6
Carolina P Bernardes, Neife A G Santos, Flavia M Sisti, Rafaela Scalco Ferreira, Norival A Santos-Filho, Adélia C O Cintra, Eduardo M Cilli, Suely V Sampaio, Antonio C Santos
Venom small peptides that target neurotrophin receptors might be beneficial in neurodegeneration, including Parkinsońs disease (PD). Their small size, ease of synthesis, structural stability and target selectivity make them important tools to overcome the limitations of endogenous neurotrophins as therapeutic agents. Additionally, they might be optimized to improve resistance to enzymatic degradation, bioavailability, potency and, mainly, lipophilicity, important to cross the blood brain barrier (BBB). Here, we evaluated the neuroprotective effects and mechanisms of the synthetic snake-venom-based peptide p-BTX-I (Glu-Val-Trp) in PC12 cells treated with MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that induces Parkinsonism in vivo...
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29659380/effect-of-pioglitazone-and-simvastatin-in-lipopolysaccharide-induced-amyloidogenesis-and-cognitive-impairment-in-mice-possible-role-of-glutamatergic-pathway-and-oxidative-stress
#7
Sara Thabit, Nesrine S E El Sayed
Neuroinflammation and β-amyloid (Aβ) deposition in the brain are well known characteristics of neurodegeneration. Diabetes and hypercholesterolemia are the main risk factors leading to memory loss and cognitive impairment. Recently, it was found that statins and thiazolidinediones have promising anti-inflammatory and neuroprotective effects that could delay neurodegeneration and neuronal loss in diabetic and hypercholesterolemic patients. The aim of the present study was to investigate the protective effect of simvastatin, pioglitazone, and their combination in lipopolysaccharide (LPS)-induced neuroinflammation and amyloidogenesis...
April 13, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29649746/degradation-of-alpha-synuclein-by-dendritic-cell-factor-1-delays-neurodegeneration-and-extends-lifespan-in-drosophila
#8
Shiqing Zhang, Ruili Feng, Yanhui Li, Linhua Gan, Fangfang Zhou, Shiquan Meng, Qian Li, Tieqiao Wen
Parkinson's disease (PD) is a common neurodegenerative disease associated with the progressive loss of dopaminergic neurons in the substantia nigra. Proteinaceous depositions of alpha-synuclein (α-syn) and its mutations, A30P and A53T, are one important characteristic of PD. However, little is known about their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a membrane protein that plays important roles in nerve development in mouse. In this study, we aimed to show that DCF1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth...
March 13, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29627381/restorative-effect-of-l-dopa-treatment-against-ochratoxin-a-induced-neurotoxicity
#9
Pratiksha V Bhat, T Anand, Manu T Mohan, Farhath Khanum
The toxic effects of Ochratoxin A (OTA), a fungal secondary metabolite of the genera Aspergillus and Penicillium with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) a Parkinson inducing drug were investigated to evaluate the neurotoxic effects exerted by OTA. OTA is known to contaminate food and feedstuff leading to a wide range of toxicity like nephrotoxicity, hepatotoxicity, and immunotoxicity. However, due to the dearth of available information on the possible mechanisms of OTA neurotoxicity and neurodegeneration the current study was undertaken...
April 5, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29589441/marbostat-100-defines-a-new-class-of-potent-and-selective-antiinflammatory-and-antirheumatic-histone-deacetylase-6-inhibitors
#10
Andreas Sellmer, Hubert Stangl, Mandy Beyer, Elisabeth Grünstein, Michel Leonhardt, Herwig Pongratz, Emerich Eichhorn, Sigurd Elz, Birgit Striegl, Zsuzsa Jenei-Lanzl, Stefan Dove, Rainer H Straub, Oliver H Krämer, Siavosh Mahboobi
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammatory, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects...
March 28, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29587458/towards-an-integrative-understanding-of-trna-aminoacylation-diet-host-gut-microbiome-interactions-in-neurodegeneration
#11
Elena L Paley, George Perry
Transgenic mice used for Alzheimer's disease (AD) preclinical experiments do not recapitulate the human disease. In our models, the dietary tryptophan metabolite tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase (TrpRS) deficiency with consequent neurodegeneration in cells and mice. Dietary supplements, antibiotics and certain drugs increase tryptamine content in vivo. TrpRS catalyzes tryptophan attachment to tRNAtrp at initial step of protein biosynthesis. Tryptamine that easily crosses the blood-brain barrier induces vasculopathies, neurodegeneration and cell death via TrpRS competitive inhibition...
March 26, 2018: Nutrients
https://www.readbyqxmd.com/read/29561730/improved-serotonergic-neurotransmission-by-genistein-pretreatment-regulates-symptoms-of-obsessive-compulsive-disorder-in-streptozotocin-induced-diabetic-mice
#12
Pradeep Phadnis, Purnima Dey Sarkar, Mithun Singh Rajput
BACKGROUND: Initial evidences have shown that diabetes mellitus occurs concomitantly with obsessive-compulsive disorder (OCD) symptomatology. Serotonergic psychiatric therapy posits that serotonin is a central character in the management of OCD. Hence, it is worth investigating novel chemical entities affecting the serotonergic system for targeting OCD. An isoflavonoid phytoestrogen, genistein, has been recognized as of great pharmacological value especially for protecting neurodegeneration, depression (serotonin regulation), and diabetes...
March 21, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29510692/are-dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-the-same-disease
#13
Kurt A Jellinger, Amos D Korczyn
BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which share many clinical, neurochemical, and morphological features, have been incorporated into DSM-5 as two separate entities of major neurocognitive disorders with Lewy bodies. Despite clinical overlap, their diagnosis is based on an arbitrary distinction concerning the time of onset of motor and cognitive symptoms, namely as early cognitive impairment in DLB and later onset following that of motor symptoms in PDD...
March 6, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29497113/tolerance-of-chronic-hdaci-treatment-for-neurological-visceral-and-lung-niemann-pick-type-c-disease-in-mice
#14
Md Suhail Alam, Bruce Cooper, Joseph D Farris, Kasturi Haldar
Histone deacetylase (HDAC) inhibitors are of significant interest as drugs. However, their use to treat neurological disorders has raised concern because HDACs are required for brain function. We have previously shown that a triple combination formulation (TCF) of the pan HDACi vorinostat (Vo), 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and polyethylene glycol (PEG) 400 improves pharmacokinetic exposure and entry of Vo into the brain. TCF treatment significantly delayed both neurodegeneration and death in the Npc1 nmf164 murine model of Niemann-Pick Type C (NPC) disease...
March 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29471022/temporal-lobe-epilepsy-induced-neurodegeneration-and-cognitive-deficits-implications-for-aging
#15
REVIEW
M Vrinda, S Arun, B N Srikumar, Bindu M Kutty, B S Shankaranarayana Rao
Epilepsy is a neurological condition associated with seizures, neurodegeneration, circuit reorganization, and other structural and functional abnormalities. These elements ultimately lead to behavioural alterations such as anxiety, depression, and importantly cognitive impairment like learning disability and memory impairment. These factors can attribute to acceleration of aging and cognitive impairment in middle-aged people, which is otherwise evident in dementia and Alzheimer's disease among elderly people...
February 19, 2018: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/29468563/neurobiological-correlates-of-alpha-tocopherol-antiepileptogenic-effects-and-microrna-expression-modulation-in-a-rat-model-of-kainate-induced-seizures
#16
Patrizia Ambrogini, Maria Cristina Albertini, Michele Betti, Claudia Galati, Davide Lattanzi, David Savelli, Michael Di Palma, Stefania Saccomanno, Desirée Bartolini, Pierangelo Torquato, Gabriele Ruffolo, Fabiola Olivieri, Francesco Galli, Eleonora Palma, Andrea Minelli, Riccardo Cuppini
Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings allowed us to postulate an antiepileptogenic potential for α-T in hippocampal excitotoxicity, in line with clinical evidence showing that α-T improves seizure control in drug-resistant patients...
February 22, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29462693/two-novel-dual-glp-1-gip-receptor-agonists-are-neuroprotective-in-the-mptp-mouse-model-of-parkinson-s-disease
#17
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29436598/madecassoside-activates-anti%C3%A2-neuroinflammatory-mechanisms-by-inhibiting-lipopolysaccharide%C3%A2-induced-microglial-inflammation
#18
Andrew Octavian Sasmita, Anna Pick Kiong Ling, Kenny Gah Leong Voon, Rhun Yian Koh, Ying Pei Wong
Neurodegeneration is typically preceded by neuroinflammation generated by the nervous system to protect itself from tissue damage, however, excess neuroinflammation may inadvertently cause more harm to the surrounding tissues. Attenuating neuroinflammation with non‑steroidal anti‑inflammatory drugs can inhibit neurodegeneration. However, such treatments induce chronic side effects, including stomach ulcers. Madecassoside, a triterpene derived from Centella asiatica, is considered to be an alternative treatment of inflammation...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29426225/high-content-microfluidic-screening-platform-used-to-identify-%C3%AF-2r-tmem97-binding-ligands-that-reduce-age-dependent-neurodegeneration-in-c-elegans-sc_app-model
#19
Sudip Mondal, Evan Hegarty, James J Sahn, Luisa L Scott, Sertan Kutal Gökçe, Chris Martin, Navid Ghorashian, Praveen Navoda Satarasinghe, Sangeetha Iyer, Wisath Sae-Lee, Timothy R Hodges, Jonathan T Pierce, Stephen F Martin, Adela Ben-Yakar
The nematode Caenorhabditis elegans, with tractable genetics and a well-defined nervous system, provides a unique whole-animal model system to identify novel drug targets and therapies for neurodegenerative diseases. Large-scale drug or target screens in models that recapitulate the subtle age- and cell-specific aspects of neurodegenerative diseases are limited by a technological requirement for high-throughput analysis of neuronal morphology. Recently, we developed a single-copy model of amyloid precursor protein (SC_APP) induced neurodegeneration that exhibits progressive degeneration of select cholinergic neurons...
February 23, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29424466/differential-local-tissue-permissiveness-influences-the-final-fate-of-gpr17-expressing-oligodendrocyte-precursors-in-two-distinct-models-of-demyelination
#20
Giusy T Coppolino, Davide Marangon, Camilla Negri, Gianluca Menichetti, Marta Fumagalli, Paolo Gelosa, Leda Dimou, Roberto Furlan, Davide Lecca, Maria P Abbracchio
Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2 xCAG-eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult...
May 2018: Glia
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