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CNS & Neurological Disorders Drug Targets

Barcutean Laura Iulia, Romaniuc Andreea, Maier Smaranda, Bajko Zoltan, Motataianu Anca, Hutanu Adina, Simu Iunius, Andone Sebastian, Balasa Rodica
Introduction We evaluated the peripheral immune panel of multiple sclerosis (MS) patients treated for more than 10 years with interferon-beta1b (IFNβ-1b) and aimed to identify possible biomarkers of treatment response. Material and Methods Serum samples from 70 MS patients treated with IFNβ-1b more than a decade were analysed for 15 cytokines, that were correlated with the disability score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapses on treatment-ARR_1 and demographic data. Two groups were defined based on the levels of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 - recurrent-remissive and G2 - secondary-progressive...
September 16, 2018: CNS & Neurological Disorders Drug Targets
Arturo Solís Herrera, Ghulam Md Ashraf, Maria Del Carmen Arias Esparza, Vadim V Tarasov, Vladimir N. Chubarev, Marco F. Avila-Rodriguez, Alfiya Makhmutovа, Magdah Ganash, Abdul Hafeez, Sergey O Bachurin, Gjumrakch Aliev
Regulation of composition, volume and turnover of fluids surrounding the brain and damp cells is vital. These fluids transport all substances required for cells and remove the unwanted materials. This regulation tends to act as barriers to prevent free exchange of materials between the brain and blood. There are specific mechanisms concerned with fluid secretion of the controlled composition of the brain, and others responsible for reabsorption eventually to blood and the extracellular fluid whatever their compositions...
September 3, 2018: CNS & Neurological Disorders Drug Targets
Xiaolin Deng, Yangmei Xie, Yinghui Chen
Epilepsy is a common and serious chronic neurological disorder that is mainly treated with antiepileptic drugs (AEDs). Although current AEDs used in clinical practice have developed into the third generation, approximately one-third of the patients are drug-resistant. More efficacious treatments for medication drug-resistant epilepsy (DRE) are therefore needed. Better understanding of the mechanism underlying DRE is likely to facilitate to develop a more effective therapy. Neuroinflammation has been proposed as a possible causative factor in the pathogenesis of epilepsy...
August 28, 2018: CNS & Neurological Disorders Drug Targets
Marianna Mazza, Giuseppe Marano, Gianandrea Traversi, Valentina Carocci, Benedetta Romano, Luigi Janiri
BACKGROUND: Cariprazine is a piprazine derivative approved by the FDA in 2015 for the treatment of schizophrenia and bipolar manic or mixed episodes in adults. High affinity for D3 dopamine receptors and observed actions on 5HT1A, 5HT2A and alpha 1B receptors differentiate it pharmacologically from other antipsychotics. METHOD: This review is a comprehensive and thorough summary of the most important findings on cariprazine use in bipolar mania and depression. Pharmacokinetics, pharmacogenetics, tolerability and safety adverse effects are discussed in this paper...
August 28, 2018: CNS & Neurological Disorders Drug Targets
Fatemeh Mohammadi, Navid Nezafat, Manica Negahdaripour, Fatemeh Dabbagh, Afshin Borhani Haghghi, Sedigheh Kianpour, Mehrzad Banihashemi, Younes Ghasemi
Heat shock proteins (HSPs) increases in response to many stresses in cells. Stroke is a neural shock that leads to destruction of a large number of brain cells, whereas induction and expression of HSPs can decrease the amount of damage, and in some conditions can cure damaged cells. HSP70 family is considered as the most important member of HSPs in normal and stress condition of cells. They are strongly up-regulated by stresses, and have protective roles in under stressed cells. Therefore, in this review we briefly consider the association between HSP70 and stroke...
August 26, 2018: CNS & Neurological Disorders Drug Targets
Ambreen Fatima, Smita Jyoti, Yasir Hasan Siddique
Parkinson's disease is the second most common neurodegenerative disorder affecting more than 1% of the population average 60. The majority of PD cases are sporadic and are probably caused by a combination of risk factors but 5-10% of the PD cases are familial. Due to the high degree of gene conservation between humans, mice and insects using animal model system is a valuable approach to further elucidate the roles of the genes in PD. The present review highlights the models use to study PD symptoms with special emphasis on Drosophila...
August 20, 2018: CNS & Neurological Disorders Drug Targets
Clayton Peixoto, Antonio Jose Grande, Mariana Mallmann, Antonio Egidio Nardi, Adriana Cardoso, Andre Barciela Veras
BACKGROUND: Depression is a mental disorder that affects a large part of the world's population. DHEA is a hormone that has long been attributed to the ability to improve depressive symptoms. However, few studies were conducted with depression individuals not resulting from other medical conditions. OBJECTIVE: To investigate whether DHEA is more effective than placebo in the treatment of depressive symptoms in subjects with depression not resulting from other psychiatric or medical comorbidities...
August 17, 2018: CNS & Neurological Disorders Drug Targets
Mona Askar, Abdelaziz M Hussein, Soheir Al-Basiony, Refka Meseha, Emile Metias, Mohamed Salama, Ashraf Antar, Aya El Sayed
In this study we aimed to investigate and to compare the effects of ferulic acid (FR), muscle exercise (Ex) and combination of them on rotenone (ROT)-induced Parkinson disease (PD) in mice as well as their underlying mechanisms. Thirty five male C57BL/6 mice were allocated into 5 equal groups, 1) Normal control (CTL) group, 2) ROT group (rats received ROT 3 mg/Kg i.p. for 70 days), 3) FR group (rats received ROT + FR at 20 mg/kg/day), 4) Ex group (rats received ROT + swimming Ex) and 5) FR+Ex group (rats received ROT + FR and Ex)...
August 15, 2018: CNS & Neurological Disorders Drug Targets
Jiaqi Li, Yuzhi Zhou, Guanhua Du, Xuemei Qin, Li Gao
Background Aging is a complex process accompanied with the decline of the different physiological functions. Numerous differentially expressed genes (DEGs) have been found in the aging brain of senescence-accelerated mouse P8 (SAMP8), however, it was challenging to screen out the crucial ones. Objective This study aimed to explore the crucial genes and pathways in aging brain of SAMP8 mice, which would be beneficial for understanding the pathogenesis of brain aging. Method Firstly, 430 genes that are differentially expressed in SAMP8 mice versus SAMR1 mice were obtained from 9 gene expression studies, and gene-gene network was constructed...
August 15, 2018: CNS & Neurological Disorders Drug Targets
Ashutosh Kumar, Amruta Dhawan, Akshada Shinde
Cellular physiology and energy metabolism is maintained by the constant supply of energy furnished by the powerhouses of the cell called mitochondria. Cellular homeostasis depends on the timely clearance of damaged cellular organelles and proteins via pathways including autophagy. Mitochondria and mitochondrial autophagy play a vital role in cellular health and failure of these pathways can have devastating effect on cellular homeostasis. Amongst the various cell types, neuronal cells are more vulnerable to bioenergetic depletion since most of their functions critically depend upon the availability of energy derived from mitochondrial metabolism, thus making neurodegenerative disorders an obstinate issue...
August 15, 2018: CNS & Neurological Disorders Drug Targets
Nandkishor K Mule, Jitendra Narain Singh
Diabetes and neurodegenerative diseases (ND) are progressive morbidities and in themselves represent a major public health burden. A growing body of evidence points towards the comorbidity of diabetes and NDs with a possible exacerbation of latter by former. Considering the high prevalence of both morbidities in aging world population, even a modest impact of diabetes on NDs could lead to significant public health implications. Several hypotheses and mechanistic evidence were proposed linking altered glucose metabolism to the risk of progressive dementia...
August 8, 2018: CNS & Neurological Disorders Drug Targets
Ling Li, Zuoxiao Li
BACKGROUND: T follicular helper cells (Tfh) could help B cells induce humoral immunity response. Follicular regulatory T cells (Tfr) could inhibit the activity of Tfh cells effectively and .,the two kinds of cells are in a dynamic balance.. Tofacitinib is a selective inhibitor of Jak1 and Jak3 and was approved for treating moderate to severe rheumatoid arthritis. It has proved that tofacitinib could effectively dampen the severity and progression of experimental autoimmune encephalomyelitis (EAE) by a decrease of Th1/Th17 cells and an increase in Tregs...
July 25, 2018: CNS & Neurological Disorders Drug Targets
Viktor S Kokhan, Tat'yana G Kokhan, Anna N Samsonova, Vladimir P Fisenko, Aleksey A Ustyugov, Gjumrakch Aliev
It was previously shown that inactivation of gamma-synuclein which is a small soluble neuronal protein affects psycho-emotional status and cognitive abilities in knock-out mice; yet, it was unclear what mechanisms were involved. Here, we used the passive avoidance test and acute amphetamine administration in aging gamma-synuclein knock-out mice. As a result, we found moderate aging-unlinked deficit of the dopaminergic neurotransmitter system in gamma-synuclein knock-out animals. At the same time, the evidence of elongation of the reaction time on the amphetamine administration under aging process was obtained...
July 25, 2018: CNS & Neurological Disorders Drug Targets
Nurul 'Ain Arshad, Teoh Seong Lin, Mohamad Fairuz Yahaya
Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease...
July 24, 2018: CNS & Neurological Disorders Drug Targets
Xiao-Wen Jiang, Hong-Yuan Lu, Ziru Xu, Tian-Yi Liu, Qiong Wu, Yue Yang, Qing-Chun Zhao, Hui-Yuan Gao
BACKGROUND: Epilepsy and Alzheimer's disease are common neuropathies with complex pathogenesis. Both of them have some correlations in etiology, pathogenesis, pathological changes, clinical manifestations, and treatment. OBJECTIVE: This study investigated the key genes and molecular genetic mechanism in epilepsy and Alzheimer's disease by bioinformatics analysis. METHOD: Two gene expression profiles were used to screen differentially expressed genes by GEO2R tool...
July 24, 2018: CNS & Neurological Disorders Drug Targets
Heidi Ormstad, Vesna Bryn, Robert Verkerk, Ola H Skjeldal, Bente Halvorsen, Ola Didrik Saugstad, Jorn Isaksen, Michael Maes
BACKGROUND: There is evidence that changes in neuro-immune responses coupled with dysfunctions in serotonin metabolism underpin the pathophysiology of autism spectrum disorders (ASD). OBJECTIVE: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism. METHODS: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included...
July 20, 2018: CNS & Neurological Disorders Drug Targets
Lucia Chico, Elena Caldarazzo Ienco, Costanza Bisordi, Annalisa Lo Gerfo, Lucia Petrozzi, Antonio Petrucci, Michelangelo Mancuso, Gabriele Siciliano
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to motoneurons degeneration. To date, there is no effective treatment against this disease, so several compounds have been tested aimed to improve the course of ALS, acting on its pathogenic mechanisms. In the last years, a great interest has been dedicated to studying the effects of curcumin, a natural compound that acts modulating mitochondrial functions and oxidative stress. OBJECTIVE: To investigate the efficacy of curcumin oral supplementation (600 mg/day, Brainoil) in a double-blind randomized pilot trial (for the first three months), followed by an open-label phase (for the last three months), on clinical parameters and biochemical markers, in 42 ALS patients...
July 20, 2018: CNS & Neurological Disorders Drug Targets
Hussein Kadhem Al-Hakeim, Sadiq Neama Al-Kufi, Arafat Hussein Al-Dujaili, Michael Maes
Major depressive disorder (MDD), has been associated with inflammatory processes, including increased cytokine levels, even in individuals who are otherwise physically healthy, while some MDD patients may show insulin resistance (IR). However, correlations between cytokines and IR parameters have not been studied extensively in MDD. In the present study, we measured IL-1β, IL-4, IFN-γ, TGF-β1, insulin and glucose in 63 MDD patients and 27 healthy controls. The associations between cytokine levels and IR were examined...
July 20, 2018: CNS & Neurological Disorders Drug Targets
Hamidreza Famitafreshi, Morteza Karimian
Autism is a developmental disorder that manifests itself in early childhood. Autism is characterized by inability to acquire social skills, repetitive behaviors and failure of speech and nonverbal communication development. Recent studies have shown that genetic mutations occur in majority of individuals with autism. These mutations cause a variety of disorders that ultimately lead to brain disorders. It is noteworthy that all mutation do not follow the same pattern. They encompass various kinds of mutations...
July 6, 2018: CNS & Neurological Disorders Drug Targets
Ajeet Singh, Abshar Hasan, Sakshi Tiwari, Lalit M Pandey
Over the last two decades, Alzheimer disease (AD) associated research has accomplished an overwhelming momentum, as it is one of the major current healthcare issues in the developed world. AD is characterized by the presence of Aβ mediated extracellular amyloid fibrils and tau-mediated intracellular neurofibrillar tangles and reports highlight their subsequent effects on neuronal synaptic activity, antioxidant response and recently explored mitochondrial dysfunction. Additionally, recent reports have demonstrated the mitochondrial dysfunction and associated physiological as well as cellular alterations triggered by fibrillar structures inside the brain tissue...
June 27, 2018: CNS & Neurological Disorders Drug Targets
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