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CNS & Neurological Disorders Drug Targets

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https://www.readbyqxmd.com/read/28325153/ultra-micronized-palmitoylethanolamide-an-efficacious-adjuvant-therapy-for-parkinson-s-disease
#1
Stefania Brotini, Carlo Schievano, Leonello Guidi
BACKGROUND: Parkinson's disease (PD) is the subject of intense efforts to develop strategies that slow down or stop disease progression and disability. Substantial evidence points to a prominent role for neuroinflammation in the underlying dopaminergic cell death. Ultramicronized palmitoylethanolamide (um-PEA) is well-known for its ability to promote the resolution of neuroinflammation and exert neuroprotection. This study was designed to assess the efficacy of um-PEA as adjuvant therapy in patients with advanced PD...
March 21, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28322171/dopaminergic-modulation-of-sleep-wake-states
#2
Andrea Herrera-Solís, Wendy Herrera-Morales, Luis Núñez-Jaramillo, Oscar Arias-Carrión
The role of dopamine in sleep-wake regulation is associated as a wakefulness-promoting agent. For the clinical treatment of excessive daytime sleepiness, drugs have been commonly used to increase dopamine release. However, sleep disorders or lack of sleep is related to several dopamine-related disorders. The effects of dopaminergic agents, nevertheless, are mediated by two families of dopamine receptors, D1 and D2-like receptors; the first family increases adenylyl cyclase activity and the second inhibits adenylyl cyclase...
March 20, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28322170/utilizing-delta-opioid-receptors-and-peptides-for-cytoprotection-implications-in-stroke-and-other-neurological-disorders
#3
Marci G Crowley, M Grant Liska, Trenton Lippert, Sydney Coreya, Cesar V Borlongan
The opioid system has been elucidated as a potential target for therapy in a variety of neurological disorders including stroke. Delta opioid receptors have been revealed to pose an especially compelling biological function for new neuroprotective therapies. Two distinct therapeutic mechanisms have been characterized for delta opioid receptors s, namely, these receptors aid in maintaining ionic homeostasis and initiate endogenous neuroprotective pathways. Specific agonists of delta opioid receptors, such as (D-Ala2, D-Leu5) enkephalin (DADLE), have displayed the ability to promote neuronal survival and mitigate apoptotic pathways...
March 20, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28294051/further-evaluation-of-mechanisms-associated-with-the-antidepressant-like-signature-of-scopolamine-in-mice
#4
Anna E Martin, Douglas A Schober, Alexander Nikolayev, Vladimir V Tolstikov, Wesley H Anderson, Richard E Higgs, Ming-Shang Kuo, Anastasia Laksmanan, John T Catlow, Xia Li, Christian C Felder, Jeffrey M Witkin
Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling...
March 9, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28260511/clinically-relevant-drug-interactions-with-anti-alzheimer-s-drugs
#5
Filippo Caraci, Janet Sultana, Filippo Drago, Edoardo Spina
The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD...
March 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28240190/demonstration-of-biological-and-immunological-equivalence-of-a-generic-glatiramer-acetate
#6
Josephine D D Alessandro, Kevin Garofalo, Ganlin Zhao, Christopher Honan, Jay Duffner, Ishan Capila, Ian Fier, Ganesh Kaundinya, Daniel Kantor, Tanmoy Ganguly
In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone. In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, antigen-presenting cell biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28240189/suicide-prevention-in-schizophrenia-do-long-acting-injectable-antipsychotics-lais-have-a-role
#7
Maurizio Pompili, Laura Orsolini, Dorian A Lamis, David R Goldsmith, Adele Nardella, Giulia Falcone, Valentina Corigliano, Mario Luciano, Andrea Fiorillo
Suicide risk is a major cause of death among patients with schizophrenia. Death by suicide has been reported in approximately 5% of schizophrenia patients although such figure appears an underestimation of the problem. A number of risk factors are routinely reported as associated with suicide risk among these patients, some of which are modifiable by targeted therapeutic strategies. Clozapine is the only compound that gathered evidence as an effective treatment for reducing suicide risk in schizophrenia. Long-Acting Injectable Antipsychotics (LAIs) have a range of advantages in terms of efficacy, safety and tolerability in the treatment of schizophrenia, and one area of interest is whether LAI-treatment may decrease suicidality by indirectly acting on a range of risk factors for suicide specific to schizophrenia patients...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28240188/parkinson-s-disease-is-accompanied-by-intertwined-alterations-in-iron-metabolism-and-activated-immune-inflammatory-and-oxidative-stress-pathways
#8
Michael Maes, Carine Coneglian De Farias, Kamila Landucci Bonifácio, Andressa Keiko Matsumoto, Chiara Cristina Bortolasci, André de Souza Nogueira, Francis Fregonesi Brinholi, Helena Kaminami Morimoto, Lucio Baena de Melo, Estefânia Gastaldello Moreira, Décio Sabbatini Barbosa
BACKGROUND: Parkinson's diasease (PD) is a neurodegenerative disorder characterized by a complex interplay between peripheral and central inflammatory and oxidative stress pathways. OBJECTIVE: To investigate immune-inflammatory and oxidative stress pathways in relation to iron metabolism in peripheral blood of PD patients and healthy controls. METHODS: We recruited 56 healthy individuals and 56 PD patients in stages 1-3 of Hoehn and Yahr Scale...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28240187/the-endocannabinoid-system-modulating-levels-of-consciousness-emotions-and-likely-dream-contents
#9
Eric Murillo-Rodriguez, José Carlos Pastrana-Trejo, Mireille Salas-Crisóstomo, Miriel de-la-Cruz
Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is ∆9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors. These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28176642/granulocyte-colony-stimulating-factor-attenuates-blood-brain-barrier-damage-and-improves-cognitive-function-in-spontaneously-hypertensive-rats
#10
Xin Wei, Yan Xu, Yanling Jin, Hongliang Feng, Shouquan Dong
Cerebral small vessel diseases (CSVDs) always coincide with endothelial dysfunction and blood-brain barrier (BBB) damage. Granulocyte-colony stimulating factor (G-CSF) can play a neuroprotective role in many neurological diseases. We investigated whether G-CSF exerts positive effects in spontaneously hypertensive rats (SHRs), a rat model of CSVD. Twenty-four-week-old SHRs, displaying the early histopathological changes of CSVD, received daily administrations of either G-CSF (50μg/kg) or saline for 7 days. The novel object recognition test was then conducted after treatment...
February 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28176641/gabaa-receptors-as-targets-for-the-management-of-pain-related-disorders
#11
Bradford D Fischer
Chronic pain is most commonly treated with opioid analgesics, anti-inflammatory steroids, and nonsteroidal anti-inflammatory drugs; although the clinical use of these compounds are constrained by unwanted side effects. GABAergic neurons are located in spinal nociceptive circuits suggesting that drugs with affinity at these receptors, including benzodiazepine-like drugs, may provide an alternative to opioids for the treatment of pain. However, systemically administered conventional benzodiazepines fail to produce antihyperalgesic effects, likely due to their concurrent sedative properties...
February 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28176640/inhibition-of-butyrylcholinesterase-with-fluorobenzylcymserine-an-experimental-alzheimer-s-drug-candidate-validation-of-enzoinformatics-results-by-classical-and-innovative-enzyme-kinetic-analyses
#12
Mohammad Amjad Kamal, Shazi Shakil, Muhammad S Nawaz, Qian-Sheng Yu, Harold W Holloway, Y Tan, Xianqin Qu, Nigel H Greig
Selective butyrylcholinesterase (BuChE)-inhibition, increases acetylcholine (ACh) levels. In rodents, this inhibition is known to boost cognition. Also, this occurs without the typical unwanted effects of acetylcholinesterase-inhibitors or AChE-Is. The novel compound, fluorobenzylcymserine (FBC), is derived from our effort to design a selective BuChE-inhibitor. Also, we wanted to check whether butyrylcholinesterase-inhibitors (BuChE-Is) possessed an edge over AChE-Is in Alzheimer's disease (AD) in terms of efficacy and/or tolerance...
February 7, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28176622/the-tlr9-antagonist-icpg-odn-at-different-dosages-inhibits-cerebral-ischemia-reperfusion-injury-in-mice
#13
Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong Dong, Lingna Deng Deng, Yidong Wang
Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear. This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion. Neurological function, infarct size, splenocytes and the expression of TLR9 and the downstream products of the TLR9 pathways were determined after cerebral I/R for up to 72 hours...
February 6, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28124620/monoamine-oxidase-b-inhibitors-in-parkinson-s-disease
#14
Livia Dézsi, László Vécsei
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. OBJECTIVE: To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials...
January 24, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28124619/the-effect-of-pyrroloquinoline-quinone-on-apoptosis-and-autophagy-in-traumatic-brain-injury
#15
Pengju Zhang, Yongqi Ye, Yuhang Qian, Baoxin Yin, Jianmei Zhao, Shunxin Zhu, Li Zhang, Meijuan Yan
BACKGROUND: Pyrroloquinoline quinoe is an anionic, water-soluble compound with antioxidant characteristic. The role of pyrroloquinoline quinoe in pharmacology and nutrition has attracted wide attention of researchers. Although a few experiments have confirmed that pyrroloquinoline quinoe plays an obvious effective role in neuroprotection. There are little reports about the effect of pyrroloquinoline quinoe in traumatic brain injury. Traumatic brain injury is one of the leading causes of adult disability and death in the world...
January 24, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28124618/alzheimer-s-disease-and-the-routine-clinical-use-of-csf-biomarkers
#16
Alessandro Martorana
Amyloid based hypothesis led to develop biomarkers oriented diagnosis of neurodegenerative dementias. Among them biomarkers for AD, the most diffuse form of dementia, are currently the unique available for scientific and diagnostic purposes. CSF biomarkers like Amyloid beta 42, total tau and phosphorylated tau levels can be easily evaluated in individuals suffering from cognitive decline, to diagnose or exclude AD type dementia, since early stages. Moreover, their analysis gave the opportunity to better understand cognitive decline patho-physiology during aging...
January 24, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28124605/increase-signaling-of-wnt-%C3%AE-catenin-pathway-and-presence-of-apoptosis-in-cerebellum-of-kindled-rats
#17
Carmen Rubio-Osornio, Artemio Rosiles-Abonce, Cristina Trejo-Solís, Moisés Rubio-Osornio, Cesar Mendoza, Verónica Custodio, Juan Carlos Martínez-Lazcano, Edith González, Carlos Paz
Epilepsy is one of the most common neurological disorders in humans, and the role of the cerebellum in its physiopathology remains the subject of study. The Purkinje cells (PC), whose axons target the dentate and interpositus nuclei, form the main cerebellar output to forebrain structures involved in epilepsy. Cerebellar atrophy related to loss of PC has been reported in chronic epilepsy although its mechanism remains unclear. Taking in account that an overexpression of β-Catenin has been related with cell death, here we present the signaling of β-Catenin and the type of PC death in cerebellum of rats with chronic seizures induced by the amygdaloid kindling model...
January 17, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28124604/the-interplay-between-cofilin-and-phospho-cofilin-its-role-in-maintaining-blood-brain-barrier-integrity
#18
Qasim Alhadidi, Muhammad Shahdaat Bin Sayeed, Zahoor Shah
The blood brain barrier (BBB) is a continuous, non-fenestrated vessel system that tightly regulates the movement of molecules, ions, and cells between the blood and the central nervous system. Endothelial cells are the major constituents of the BBB and these cells are linked to each other through intercellular contact points composed of tight junctions, adherent junctions and gap junctions. These three types of junctions are connected to the intracellular actin cytoskeleton via various adaptor proteins. Thus, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts and vascular permeability...
January 17, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28088901/advanced-structure-activity-relationships-applied-to-mentha-spicata-l-subsp-spicata-essential-oil-compounds-as-ache-and-nmda-ligands-in-comparison-with-donepezil-galantamine-and-memantine-new-approach-in-brain-disorders-pharmacology
#19
Speranta Avram, Mernea Maria, Eyup Bagci, Lucian Hritcu, Livia-Cristina Borcan, Dan Mihailescu
BACKGROUND: Alzheimer's disease (AD) therapy is based on several natural and synthetic compounds that act as acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands that have limited efficiency in relieving AD symptoms. Recent studies show that inhibitors isolated from Mentha spicata L. subsp. spicata are promising for AD therapy. OBJECTIVE: We aimed to identify novel and more potent phytopharmaceutical compounds for AD treatment by taking into account the compounds from Mentha spicata L...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#20
Stephen D Skaper, Laura Facci, Morena Zusso, Pietro Giusti
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
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