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Drug induced neurodegeneration

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https://www.readbyqxmd.com/read/28435263/neuroprotection-against-apoptosis-of-sk-n-mc-cells-using-rmp-7-and-lactoferrin-grafted-liposomes-carrying-quercetin
#1
Yung-Chih Kuo, Chien-Wei Tsao
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#2
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28396435/intranasal-msc-derived-a1-exosomes-ease-inflammation-and-prevent-abnormal-neurogenesis-and-memory-dysfunction-after-status-epilepticus
#3
Qianfa Long, Dinesh Upadhya, Bharathi Hattiangady, Dong-Ki Kim, Su Yeon An, Bing Shuai, Darwin J Prockop, Ashok K Shetty
Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrow-derived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#4
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28377426/alterations-in-endo-lysosomal-function-induce-similar-hepatic-lipid-profiles-in-rodent-models-of-drug-induced-phospholipidosis-and-sandhoff-disease
#5
Emmanuelle Lecommandeur, David Baker, Timothy M Cox, Andrew W Nicholls, Julian L Griffin
Drug-induced phospholipidosis (DIPL) is characterised by an increase in the phospholipid content of the cell and the accumulation of drugs and lipids inside the lysosomes of affected tissues, including in the liver. While of uncertain pathological significance for patients, the condition remains a major impediment for the clinical development of new drugs. Human Sandhoff disease (SD) is caused by inherited defects of the β subunit of lysosomal β-hexosaminidases (Hex) A and B, leading to a large array of symptoms, including neurodegeneration and ultimately death by the age of four in its most common form...
April 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28373844/effects-of-ketamine-on-levels-of-inflammatory-cytokines-il-6-il-1%C3%AE-and-tnf-%C3%AE-in-the-hippocampus-of-mice-following-acute-or-chronic-administration
#6
Yanning Li, Ruipeng Shen, Gehua Wen, Runtao Ding, Ao Du, Jichuan Zhou, Zhibin Dong, Xinghua Ren, Hui Yao, Rui Zhao, Guohua Zhang, Yan Lu, Xu Wu
Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28373076/fty720-fingolimod-regulates-key-target-genes-essential-for-inflammation-in-microglial-cells-as-defined-by-high-resolution-mrna-sequencing
#7
Amitabh Das, Sarder Arifuzzaman, Sun Hwa Kim, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Although microglial cells have an essential role in the host defense of the brain, the abnormal activation of microglia can lead to devastating outcomes, such as neuroinflammation and neurodegeneration. Emerging evidence indicates that FTY720 (fingolimod), an FDA-approved drug, has beneficial effects on brain cells in the central nervous system (CNS) and, more recently, immunosuppressive activities in microglia via modulation of the sphingosine 1 phosphate (S1P) 1 receptor. However, the exact molecular aspects of FTY720 contribution in microglia remain largely unaddressed...
March 31, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28366453/genetic-correction-of-sod1-mutant-ipscs-reveals-erk-and-jnk-activated-ap1-as-a-driver-of-neurodegeneration-in-amyotrophic-lateral-sclerosis
#8
Akshay Bhinge, Seema C Namboori, Xiaoyu Zhang, Antonius M J VanDongen, Lawrence W Stanton
Although mutations in several genes with diverse functions have been known to cause amyotrophic lateral sclerosis (ALS), it is unknown to what extent causal mutations impinge on common pathways that drive motor neuron (MN)-specific neurodegeneration. In this study, we combined induced pluripotent stem cells-based disease modeling with genome engineering and deep RNA sequencing to identify pathways dysregulated by mutant SOD1 in human MNs. Gene expression profiling and pathway analysis followed by pharmacological screening identified activated ERK and JNK signaling as key drivers of neurodegeneration in mutant SOD1 MNs...
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28322157/diabetes-related-neurological-implications-and-pharmacogenomics
#9
Rojas Carranza Camilo Andrés, Bustos Cruz Rosa Helena, Pino Pinzón Carmen Juliana, Ariza Marquez Yeimy Viviana, Gómez Bello Rosa Margarita, Cañadas Garre Marisa
Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body's inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#10
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28293774/hiv-associated-neurodegeneration-and-neuroimmunity-multivoxel-mr-spectroscopy-study-in-drug-na%C3%A3-ve-and-treated-patients
#11
Jasmina Boban, Dusko Kozic, Vesna Turkulov, Jelena Ostojic, Robert Semnic, Dajana Lendak, Snezana Brkic
OBJECTIVES: The aim of this study was to test neurobiochemical changes in normal appearing brain tissue in HIV+ patients receiving and not receiving combined antiretroviral therapy (cART) and healthy controls, using multivoxel MR spectroscopy (mvMRS). METHODS: We performed long- and short-echo 3D mvMRS in 110 neuroasymptomatic subjects (32 HIV+ subjects on cART, 28 HIV+ therapy-naïve subjects and 50 healthy controls) on a 3T MR scanner, targeting frontal and parietal supracallosal subcortical and deep white matter and cingulate gyrus (NAA/Cr, Cho/Cr and mI/Cr ratios were analysed)...
March 14, 2017: European Radiology
https://www.readbyqxmd.com/read/28292181/synthesis-structure-characterization-and-evaluation-in-microglia-cultures-of-neuromelanin-analogues-suitable-for-modeling-parkinson-s-disease
#12
Emanuele Ferrari, Andrea Capucciati, Ilaria Prada, Fabio Andrea Zucca, Giulia D'Arrigo, Daniele Pontiroli, Maria Grazia Bridelli, Michela Sturini, Luigi Bubacco, Enrico Monzani, Claudia Verderio, Luigi Zecca, Luigi Casella
In the substantia nigra of human brain, neuromelanin (NM) released by degenerating neurons can activate microglia with consequent neurodegeneration, typical of Parkinson's disease (PD). Synthetic analogues of NM were prepared to develop a PD model reproducing the neuropathological conditions of the disease. Soluble melanin-protein conjugates were obtained by melanization of fibrillated β-lactoglobulin (fLG). The melanic portion of the conjugates contains either eumelanic (EufLG) or mixed eumelanic/pheomelanic composition (PheofLG), the latter better simulating natural NMs...
March 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28280340/wheat-germ-agglutinin-conjugated-liposomes-incorporated-with-cardiolipin-to-improve-neuronal-survival-in-alzheimer-s-disease-treatment
#13
Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou
Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer's disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28276776/brain-injury-with-diabetes-mellitus-evidence-mechanisms-and-treatment-implications
#14
REVIEW
Sherifa A Hamed
Diabetes mellitus is a risk for brain injury. Brain injury is associated with acute and chronic hyperglycaemia, insulin resistance, hyperinsulinemia, diabetic ketoacidosis (DKA) and hypoglycaemic events in diabetic patients. Hyperglycemia is a cause of cognitive deterioration, low intelligent quotient, neurodegeneration, brain aging, brain atrophy and dementia. Areas covered: The current review highlights the experimental, clinical, neuroimaging and neuropathological evidence of brain injury induced by diabetes and its associated metabolic derangements...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28273839/parkinson-s-disease-from-pathogenesis-to-pharmacogenomics
#15
REVIEW
Ramón Cacabelos
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28253877/neuroprotective-and-cognitive-enhancing-effects-of-the-combined-extract-of-cyperus-rotundus-and-zingiber-officinale
#16
Chatchada Sutalangka, Jintanaporn Wattanathorn
BACKGROUND: Currently, food supplements to improve age-related dementia are required. Therefore, we aimed to determine the effect of the combined extract of Cyperus rotundus and Zingiber officinale (CP1) on the improvement of age-related dementia in rats with AF64A-induced memory deficits. METHODS: Male Wistar rats weighing 180-200 g were orally given CP1 at doses of 100, 200 and 300 mg.kg(-1) BW for a period of 14 days after bilateral intracerebroventricular administration of AF64A...
March 3, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28253260/direct-keap1-nrf2-disruption-as-a-potential-therapeutic-target-for-alzheimer-s-disease
#17
Fiona Kerr, Oyinkan Sofola-Adesakin, Dobril K Ivanov, Jemma Gatliff, Beatriz Gomez Perez-Nievas, Hélène C Bertrand, Pedro Martinez, Rebecca Callard, Inge Snoeren, Helena M Cochemé, Jennifer Adcott, Mobina Khericha, Jorge Iván Castillo-Quan, Geoffrey Wells, Wendy Noble, Janet Thornton, Linda Partridge
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28238857/asiaticoside-attenuation-of-rotenone-induced-oxidative-burden-in-a-rat-model-of-hemiparkinsonism-by-maintaining-the-phosphoinositide-mediated-synaptic-integrity
#18
Margabandhu Gopi, Vanisree Arambakkam Janardhanam
Asiaticoside (AS), a triterpenoid saponin isolated from the Indian medicinal herb Centella asiatica is known to exert a neuroprotective effect by attenuating the neurobehavioral, neurochemical and pathological changes in animal models. However, its potential neuroprotection in rotenone-induced hemiparkinsonism which implicates phospholipid-mediated neurotransmission remains unclear. Therefore, we have investigated the neuroprotective effects of AS in rat model of ROT-infused hemiparkinsonism with respect to phosphoinositides-assisted cytodynamics and synaptic function...
February 24, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28237914/apigenin-attenuates-hippocampal-oxidative-events-inflammation-and-pathological-alterations-in-rats-fed-high-fat-fructose-diet
#19
Jagan Kalivarathan, Sathiya Priya Chandrasekaran, Kalpana Kalaivanan, Vidhya Ramachandran, Anuradha Carani Venkatraman
High calorie diet promotes oxidative stress and chronic low grade inflammation that predispose to brain dysfunction and neurodegeneration. Hippocampus region of the brain has been shown to be particularly sensitive to high calorie diet. We hypothesize that apigenin (API), a flavonoid could attenuate hippocampal derangements induced by high fat-high fructose diet (HFFD). In this study, we investigated the effects of API on oxidative stress and inflammation in the hippocampus, and compared with those of sitagliptin (STG), a standard drug with neuroprotective properties...
February 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28217866/zebrafish-models-in-neuropsychopharmacology-and-cns-drug-discovery
#20
REVIEW
Kanza M Khan, Adam D Collier, Darya A Meshalkina, Elana V Kysil, Sergey L Khatsko, Tatyana Kolesnikova, Yury Yu Morzherin, Jason E Warnick, Allan V Kalueff, David J Echevarria
Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets...
February 20, 2017: British Journal of Pharmacology
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