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Drug induced neurological disorders

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https://www.readbyqxmd.com/read/28549128/atad3-gene-cluster-deletions-cause-cerebellar-dysfunction-associated-with-altered-mitochondrial-dna-and-cholesterol-metabolism
#1
Radha Desai, Ann E Frazier, Romina Durigon, Harshil Patel, Aleck W Jones, Ilaria Dalla Rosa, Nicole J Lake, Alison G Compton, Hayley S Mountford, Elena J Tucker, Alice L R Mitchell, Deborah Jackson, Abdul Sesay, Miriam Di Re, Lambert P van den Heuvel, Derek Burke, David Francis, Sebastian Lunke, George McGillivray, Simone Mandelstam, Fanny Mochel, Boris Keren, Claude Jardel, Anne M Turner, P Ian Andrews, Jan Smeitink, Johannes N Spelbrink, Simon J Heales, Masakazu Kohda, Akira Ohtake, Kei Murayama, Yasushi Okazaki, Anne Lombès, Ian J Holt, David R Thorburn, Antonella Spinazzola
Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#2
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28538662/maternal-factors-that-induce-epigenetic-changes-contribute-to-neurological-disorders-in-offspring
#3
REVIEW
Avijit Banik, Deepika Kandilya, Seshadri Ramya, Walter Stünkel, Yap Seng Chong, S Thameem Dheen
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits...
May 24, 2017: Genes
https://www.readbyqxmd.com/read/28534925/osmotin-loaded-magnetic-nanoparticles-with-electromagnetic-guidance-for-the-treatment-of-alzheimer-s-disease
#4
Faiz Ul Amin, Ali Kafash Hoshiar, Ton Duc Do, Yeongil Noh, Shahid Ali Shah, Muhammad Sohail Khan, Jungwon Yoon, Myeong Ok Kim
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain. Here, we describe for the first time the development of a new, pioneering nanotechnology-based drug delivery approach for potential therapies for neurodegenerative diseases, particularly AD. We demonstrated the delivery of fluorescent carboxyl magnetic Nile Red particles (FMNPs) to the brains of normal mice using a functionalized magnetic field (FMF) composed of positive- and negative-pulsed magnetic fields generated by electromagnetic coils...
May 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/28514890/spatial-recognition-test-a-novel-cognition-task-for-assessing-topographical-memory-in-mice
#5
Enes Havolli, Mark Dw Hill, Annie Godley, Pascal Jd Goetghebeur
Dysfunction in topographical memory is a core feature of several neurological disorders. There is a large unmet medical need to address learning and memory deficits as a whole in central nervous system disease. There are considerable efforts to identify pro-cognitive compounds but current methods are either lengthy or labour intensive. Our test used a two chamber apparatus and is based on the preference of rodents to explore novel environments. It was used firstly to assess topographical memory in mice at different retention intervals (RI) and secondly to investigate the effect of three drugs reported to be beneficial for cognitive decline associated with Alzheimer's disease, namely: donepezil, memantine and levetiracetam...
May 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#6
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28491900/screening-of-conventional-anticonvulsants-in-a-genetic-mouse-model-of-epilepsy
#7
Nicole A Hawkins, Lyndsey L Anderson, Tracy S Gertler, Linda Laux, Alfred L George, Jennifer A Kearney
OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet syndrome typically begins in infancy with seizures provoked by fever and then progresses to include afebrile pleomorphic seizure types...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28490750/dv21-decreases-excitability-of-cortical-pyramidal-neurons-and-acts-in-epilepsy
#8
Min Xu, Peng Sun, Ying Zhang, Ci-Hang Yang, Xin Wei, Xiao-Xia Ma, Chong-Ren Yang, Kun-Ming Ni, Ying-Jun Zhang, Xiao-Ming Li
Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487393/potent-thrombolytic-effect-of-n-acetylcysteine-on-arterial-thrombi
#9
Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien, Maxime Gauberti
Background -Platelet crosslinking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome or acute limb ischemia. N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and arterial recanalization...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28471848/l-borneol-induces-transient-opening-of-the-blood-brain-barrier-and-enhances-the-therapeutic-effect-of-cisplatin
#10
Yi Yin, Liu Cao, Hongfei Ge, Wangsheng Duanmu, Liang Tan, Jichao Yuan, Chen Tunan, Fei Li, Rong Hu, Fabao Gao, Hua Feng
The blood-brain barrier (BBB) protects the central nervous system from external insults by limiting substance diffusion through the endothelial interface. The presence of the BBB makes drug delivery in neurological disorders very challenging. Cisplatin has been shown to be cytotoxic to glioma cells, but substantial limitations exist in its clinical applications due to difficulties in penetration across the BBB. Here, we show that L-borneol, a messenger drug widely used in traditional Chinese medicine, can induce transient disruption of the BBB after 20 min of oral administration...
May 3, 2017: Neuroreport
https://www.readbyqxmd.com/read/28468332/neuroprotective-role-of-atractylenolide-i-in-an-in-vitro-and-in-vivo-model-of-parkinson-s-disease
#11
Sandeep More, Dong-Kug Choi
Parkinson's disease (PD) is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I) in in vivo and in vitro models of PD...
May 2, 2017: Nutrients
https://www.readbyqxmd.com/read/28456899/mesenchymal-stem-cell-derived-factors-restore-function-to-human-frataxin-deficient-cells
#12
Kevin Kemp, Rimi Dey, Amelia Cook, Neil Scolding, Alastair Wilkins
Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia...
April 29, 2017: Cerebellum
https://www.readbyqxmd.com/read/28447035/novel-therapeutic-approaches-rett-syndrome-and-human-induced-pluripotent-stem-cell-technology
#13
REVIEW
Mohan Gomathi, Vellingiri Balachandar
Recent advances in induced pluripotent stem cell (iPSC) technology target screening and discovering of therapeutic agents for the possible cure of human diseases. Human induced pluripotent stem cells (hiPSC) are the right kind of platform for testing potency of specific active compounds. Ayurveda, the Indian traditional system of medicine developed between 2,500 and 500 BC, is a science involving the intelligent formulations of herbs and minerals. It can serve as a "goldmine" for novel neuroprotective agents used for centuries to treat neurological disorders...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28433105/symptomatic-treatment-of-neurologic-symptoms-in-wilson-disease
#14
Tomasz Litwin, Petr Dušek, Anna Członkowska
Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the majority of cases, treatment with drugs that induce a negative copper balance (usually chelators or zinc salts) leads to improvements in liver function and neurologic signs. However, some patients show severe neurologic symptoms at diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient group, some neurologic deficits may persist despite adequate treatment, and further neurologic deterioration may be observed after treatment initiation...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28429899/neurotransmitter-systems-neuroanatomical-pathology-and-cell-death-in-schizophrenia-update-and-perspectives
#15
Hazael Avila-Rojas, Hugo Sandoval-Zamora, Iván Pérez-Neri
Schizophrenia is a thought disorder characterized by delusional thinking which may be accompanied by hallucinations involving any sensory modality. Schizophrenia may be associated with several neurologic and psychiatric disorders. Also, it may be induced by drugs. In spite of the similarity in psychoses symptomatology, it is unknown if it involves the same underlying neurobiologic mechanisms in those cases. Schizophrenic patients exhibit not only neuroanatomical alterations, but also, distortion of several neurotransmitter systems...
June 2016: Investigación Clínica
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#16
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28412920/neuropsychiatric-and-general-interactions-of-natural-and-synthetic-cannabinoids-with-drugs-of-abuse-and-medicines
#17
Ana Lucia Arellano, Esther Papaseit, Anna Romaguera, Marta Torrens, Magi Farré
Cannabis is the most widely used illicit drug. The two most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The THC content of cannabis has been increasing during the last years and recently appeared in the market a series of synthetic cannabinoids with potent agonist activity. Recreational users frequently combine cannabis with other drugs of abuse as alcohol, amphetamines and derivatives, nicotine and cocaine. In addition these subjects can be taking medicines for acute and chronic medical conditions...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28389336/the-activity-of-selective-sigma-1-receptor-ligands-in-seizure-models-in-vivo
#18
Edijs Vavers, Baiba Svalbe, Lasma Lauberte, Ilmars Stonans, Ilga Misane, Maija Dambrova, Liga Zvejniece
Sigma-1 receptor (Sig1R) is a ligand-regulated protein which, since its discovery, has been widely studied as a novel target to treat neurological disorders, including seizures. However, the roles and mechanisms of Sig1R in the regulation of seizures are not fully understood. The aim of the present study was to test and compare effects of often used selective Sig1R ligands in models of experimentally induced seizures. The anti-seizure activities and interactions of selective Sig1R agonist PRE-084, selective Sig1R antagonist NE-100 and novel positive allosteric Sig1R modulator E1R were evaluated in pentylenetetrazol (PTZ) and (+)-bicuculline (BIC)-induced seizure models in mice...
April 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28386329/inhibiting-endoplasmic-reticulum-stress-by-lithium-chloride-contributes-to-the-integrity-of-blood-spinal-cord-barrier-and-functional-recovery-after-spinal-cord-injury
#19
Zili He, Yulong Zhou, Qingqing Wang, Jiawei Li, Zengming Zheng, Jian Chen, Hongyu Zhang, Zhouguang Wang, Huazi Xu, Jian Xiao
Endoplasmic reticulum (ER) stress play important roles in the spinal cord injury (SCI), which including blood-spinal cord barrier (BSCB) disruption. Lithium chloride (LiCl) is a clinical drug for bipolar mood disorders and contributes to neuroprotection. This study aims to investigate the effects of LiCl on BSCB disruption and the ER stress pathway induced by spinal cord injury. We examined the integrity of the BSCB with Evans Blue dye and macrophages extravasation, measured the microvessels loss, the junction proteins degeneration, the activation ER stress, and the locomotor function recovery...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28368694/autoimmune-mediated-psychosis-a-case-of-susac-syndrome-in-a-drug-user
#20
Pablo Barrio, Mercè Balcells, Delón La Puma, Carles Gaig
OBJECTIVE: Susac syndrome, a rare disorder, is thought to be mediated by autoantibodies. One of the potential targets of these autoantibodies could be an antigen in the microvessels of the brain, the retina, and the inner ear leading to central nervous system (CNS) alterations, visual disturbances, and hearing deficits. Our aim is to expand clinicians' diagnostic options when facing psychosis due to medical conditions. METHODS: A case report was conducted for this study...
April 2017: Journal of Dual Diagnosis
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