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https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#1
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29791774/serotonergic-regulation-of-insulin-secretion
#2
REVIEW
Luis Rodrigo Cataldo Bascuñan, Claire Lyons, Hedvig Bennet, Isabella Artner, Malin Fex
The exact physiological role for the monoamine serotonin (5-HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signaling network in islets involving 5-HT is being unraveled. With more than fourteen different 5-HT receptors expressed in human islets, and receptor independent mechanisms in insulin producing β-cells, our understanding of 5-HT's regulation of insulin secretion is increasing...
May 23, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29790069/antidepressant-effects-of-the-ginsenoside-metabolite-compound-k-assessed-by-behavioral-despair-test-and-chronic-unpredictable-mild-stress-model
#3
Wu Song, Yan Guo, Shuang Jiang, Lin Wei, Zhi Liu, Xiaoyan Wang, Ying Su
Depression is a major social and health problem worldwide. Compound K (CK), an intestinal metabolite of panaxadiol ginsenosides, has been demonstrated to possess significant pharmacological effects on the central nervous system (CNS). Here, we set up this study to investigate the antidepressant effect of CK, and to explore the potential mechanisms underlying this activity. The behavioral despair model and chronic unpredictable mild stress (CUMS) model were established in mice or rats, respectively. Forced swimming test (FST), tail suspension test (TST) and locomotor activity were performed in mice, while the open-field test, food consumption and sucrose preference were assessed in rats...
May 22, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29788785/impaired-serotonin-communication-during-juvenile-development-in-rats-diminishes-adult-sperm-quality
#4
Juan Díaz-Ramos, Maribel Flores-Flores, María E Ayala, Andrés Aragón-Martínez
Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p-chloroamphetamine (PCA) (0...
May 22, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29788780/isoform-selectivity-of-harmine-conjugated-1-2-3-triazoles-against-human-monoamine-oxidase
#5
Saqlain Haider, Manal Alhusban, Narayan D Chaurasiya, Babu L Tekwani, Amar G Chittiboyina, Ikhlas A Khan
AIM: There is little information available on the monoamine oxidase isoform selectivity of N-alkyl harmine analogs, which exhibit a myriad of activities including monoamine oxidase isoform A (MAO-A), tyrosine-phosphorylation-regulated kinase (DYRK1A) and cytotoxicity to several select cancer cell lines. RESULTS: Compounds 3e and 4c exhibited an IC50 of 0.83 ± 0.03 and 0.43 ± 0.002 μM against MAO-A and an IC50 of 0.26 ± 0.04 and 0.36 ± 0.001 μM against MAO-B, respectively...
May 23, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29784925/acrylamide-acute-neurotoxicity-in-adult-zebrafish
#6
Melissa Faria, Tamar Ziv, Cristian Gómez-Canela, Shani Ben-Lulu, Eva Prats, Karen Adriana Novoa-Luna, Arie Admon, Benjamin Piña, Romà Tauler, Leobardo Manuel Gómez-Oliván, Demetrio Raldúa
Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited "depression-like" phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29782957/the-role-of-monoamines-in-the-development-of-alzheimer-s-disease-and-neuroprotective-effect-of-a-proline-rich-polypeptide
#7
Konstantin Yenkoyan, Katarine Fereshetyan, Senik Matinyan, Vergine Chavushyan, Michail Aghajanov
INTRODUCTION: We have analyzed the alterations in the brain monoaminergic system using the rat model of AD-like pathology. In addition, we have investigated potential neuroprotective effects of the hypothalamic proline-rich polypeptide (PRP-1). METHODS: Histochemical staining, HPLC, chemiluminescent and bioluminescence assays. RESULTS: The levels of monoamines in the target AD brain structures were found elevated, except serotonin, which was unaffected in both hippocampus and brainstem and decreased in frontal cortex...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#8
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29780859/monoaminergic-impairment-in-down-syndrome-with-alzheimer-s-disease-compared-to-early-onset-alzheimer-s-disease
#9
Alain D Dekker, Yannick Vermeiren, Maria Carmona-Iragui, Bessy Benejam, Laura Videla, Ellen Gelpi, Tony Aerts, Debby Van Dam, Susana Fernández, Alberto Lleó, Sebastian Videla, Anne Sieben, Jean-Jacques Martin, Rafael Blesa, Juan Fortea, Peter P De Deyn
Introduction: People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS. Methods: Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29778989/involvement-of-serotonin-in-crayfish-hematopoiesis
#10
Chadanat Noonin
Serotonin (5-HT) is a conserved monoamine neurotransmitter that has several physiological functions both in vertebrates and invertebrates. In addition to its well-known function in the central nervous system, 5-HT also participates in peripheral system. However, in crustaceans, the knowledge about peripheral functions of 5-HT is limited. In this study, a role of 5-HT in hematopoiesis in crayfish, Pacifastacus leniusculus, was investigated. The presence of 5-HT in crayfish plasma and the effect of 5-HT injection on hemocyte number were examined...
May 4, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29778944/activation-and-blockade-of-basolateral-amygdala-5-ht-6-receptor-produce-anxiolytic-like-behaviors-in-an-experimental-model-of-parkinson-s-disease
#11
Yi-Na Sun, Lu Yao, Li-Bo Li, Yong Wang, Cheng-Xue Du, Yuan Guo, Jian Liu
Although the basolateral amygdala (BLA) and serotonin6 (5-HT6 ) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT6 receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats...
May 17, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778018/phytochemistry-and-pharmacology-of-anti-depressant-medicinal-plants-a-review
#12
REVIEW
Jeanette Martins, Brijesh S
Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options...
May 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775160/site-specific-expression-of-amine-oxidases-in-breast-cancer-metastases
#13
Yoon Jin Cha, Woo Hee Jung, Ja Seung Koo
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29773951/the-role-of-neuroinflammation-and-neurovascular-dysfunction-in-major-depressive-disorder
#14
REVIEW
Sang Won Jeon, Yong-Ku Kim
Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease's pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus-pituitary-adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29773909/an-unsuspected-role-for-organic-cation-transporter-3-in-the-actions-of-amphetamine
#15
Felix P Mayer, Diethart Schmid, W Anthony Owens, Georgianna G Gould, Mia Apuschkin, Oliver Kudlacek, Isabella Salzer, Stefan Boehm, Peter Chiba, Piper H Williams, Hsiao-Huei Wu, Ulrik Gether, Wouter Koek, Lynette C Daws, Harald H Sitte
Amphetamine abuse is a major public health concern for which there is currently no effective treatment. To develop effective treatments, the mechanisms by which amphetamine produces its abuse-related effects need to be fully understood. It is well known that amphetamine exerts its actions by targeting high-affinity transporters for monoamines, in particular the cocaine-sensitive dopamine transporter. Organic cation transporter 3 (OCT3) has recently been found to play an important role in regulating monoamine signaling...
April 6, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29773358/-antidepressive-agents-and-hyponatremia-a-literature-review-and-a-case-non-case-study-in-the-french-pharmacovigilance-database
#16
Michaël Rochoy, Christina Zakhem-Stachera, Johana Béné, Christophe Berkhout, Sophie Gautier
OBJECTIVE: Most antidepressants have been associated with a risk of hyponatremia in the literature. This effect is not always reported in monographs. The aim of our study was to clarify the difference of increased risk of hyponatremia among various antidepressants. METHODS: Retrospective study of such cases/non-cases from observations recorded in the French national pharmacovigilance between 01/01/2004 and 31/12/2013. We studied all antidepressants marketed in 2014 in France, with a positive control (haloperidol) and a negative one (amoxicillin)...
March 1, 2018: Thérapie
https://www.readbyqxmd.com/read/29770151/research-on-establishment-of-abnormal-phlegmatic-syndrome-with-premature-ovarian-failure-rat-model-and-effects-of-balgham-munziq-treatment
#17
Muladili Yuemaier, Mayire Tuerhong, Abulizi Keremu, Nafeisha Kadeer, Ayiguzhali Aimaiti, Xilinguli Wushouer, Adilijiang Yiming, Xiamixinuer Yilike
This study aimed to establish and explore the biological basis of abnormal phlegmatic syndrome with premature ovarian failure (POF) model in rats based on the Uighur medicine (UM) in the first place and investigate the effects of unique herbal medicine, Balgham Munziq (BMq). Mature female Wistar rats were fed with spinach and coriander in cold and humid condition for approximately 20 weeks until abnormal phlegmatic syndrome (APS) model was established. When APS model was confirmed by Uighur medical experts, APS with POF disease rats were subdivided into APS with POF disease model group and APS with POF disease treated with BMq group; the rest of them were subdivided into APS model group and APS treated with BMq group...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29769405/%C3%AE-synuclein-stimulation-of-monoamine-oxidase-b-and-legumain-protease-mediates-the-pathology-of-parkinson-s-disease
#18
Seong Su Kang, Eun Hee Ahn, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Ivette M Sandoval, Susov Dhakal, P Michael Iuvone, Xuebing Cao, Keqiang Ye
Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29768946/neuroprotective-role-of-astroglia-in-parkinson-disease-by-reducing-oxidative-stress-through-dopamine-induced-activation-of-pentose-phosphate-pathway
#19
Kyoko Mashima, Shinichi Takahashi, Kazushi Minami, Yoshikane Izawa, Takato Abe, Naoki Tsukada, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki
Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice...
January 2018: ASN Neuro
https://www.readbyqxmd.com/read/29765503/oleuropein-aglycone-protects-against-mao-a-induced-autophagy-impairment-and-cardiomyocyte-death-through-activation-of-tfeb
#20
Caterina Miceli, Yohan Santin, Nicola Manzella, Raffaele Coppini, Andrea Berti, Massimo Stefani, Angelo Parini, Jeanne Mialet-Perez, Chiara Nediani
Age-associated diseases such as neurodegenerative and cardiovascular disorders are characterized by increased oxidative stress associated with autophagy dysfunction. Oleuropein aglycone (OA), the main polyphenol found in olive oil, was recently characterized as an autophagy inducer and a promising agent against neurodegeneration. It is presently unknown whether OA can have beneficial effects in a model of cardiac stress characterized by autophagy dysfunction. Here, we explored the effects of OA in cardiomyocytes with overexpression of monoamine oxidase-A (MAO-A)...
2018: Oxidative Medicine and Cellular Longevity
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