Keywords Drug induced neurological diso...

Drug induced neurological disorders
Shinichi Hirose, Yasuyoshi Tanaka, Mami Shibata, Yuichi Kimura, Mitsuru Ishikawa, Norimichi Higurashi, Toshiyuki Yamamoto, Eisuke Ichise, Tomohiro Chiyonobu, Atsushi Ishii
Epilepsy is among the most common neurological disorders, affecting approximately 50 million people worldwide. Importantly, epilepsy is genetically and etiologically heterogenous, but several epilepsy types exhibit similar clinical presentations. Epilepsy-associated genes are being identified. However, the molecular pathomechanisms remain largely unknown. Approximately one-third of epilepsy is refractory to multiple conventional anti-epileptic drugs (AEDs). Induced pluripotent stem cells (iPSCs) provide an excellent tool to study the pathomechanisms underlying epilepsy and to develop novel treatments...
August 3, 2020: Molecular and Cellular Neurosciences
Mami Kikegawa, Xian-Yang Qin, Tomohiro Ito, Hiromi Nishikawa, Hiroko Nansai, Hideko Sone
Stress in early life has been linked with the development of late-life neurological disorders. Early developmental age is potentially sensitive to several environmental chemicals such as alcohol, drugs, food contaminants, or air pollutants. The recent advances using three-dimensional neural sphere cultures derived from pluripotent stem cells have provided insights into the etiology of neurological diseases and new therapeutic strategies for assessing chemical safety. In this study, we investigated the neurodevelopmental effects of exposure to thalidomide (TMD); 2,2',4,4'-tetrabromodiphenyl ether; bisphenol A; and 4-hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl using a human embryonic stem cell (hESC)-derived sphere model...
August 3, 2020: International Journal of Molecular Sciences
Peter Riederer, Volker Ter Meulen
While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity...
September 2020: Journal of Neural Transmission
Oleg Makarevich, Boris Sabirzhanov, Taryn G Aubrecht, Ethan P Glaser, Brian M Polster, Rebecca J Henry, Alan I Faden, Bogdan A Stoica
DNA damage triggers cell death mechanisms contributing to neuronal loss and cognitive decline in neurological disorders, including traumatic brain injury (TBI), and as a side effect of chemotherapy. Mithramycin, which competitively targets chromatin-binding sites of specificity protein 1 (Sp1), was used to examine previously unexplored neuronal cell death regulatory mechanisms via rat primary neurons in vitro and after TBI in mice (males). In primary neurons exposed to DNA-damage-inducing chemotherapy drugs in vitro we showed that DNA breaks sequentially initiate DNA-damage responses, including phosphorylation of ATM, H2 AX and tumor protein 53 (p53), transcriptional activation of pro-apoptotic BH3-only proteins, and mitochondrial outer membrane permeabilization (MOMP), activating caspase-dependent and caspase-independent intrinsic apoptosis...
July 27, 2020: Cell Death & Disease
Imran Malik, Fawad Ali Shah, Tahir Ali, Zhen Tan, Abdullah Alattar, Najeeb Ullah, Arif-Ullah Khan, Reem Alshaman, Shupeng Li
Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countries. It is characterized by permanent or transient cerebral ischemia and it activates syndrome of pathological events such as membrane depolarization, glutamate excitotoxicity, and intracellular calcium buildup. Carveol is widely employed as anti-inflammatory and antioxidant in traditional Chinese medicine. In the present study, the neuroprotective effects of post-treated carveol were demonstrated against transient middle cerebral artery occlusion (MCAO) induced focal ischemic cerebral injury...
2020: Frontiers in Neuroscience
Vinita Bharat, Xinnan Wang
Parkinson's disease (PD) is a debilitating movement disorder, significantly afflicting the aging population. Efforts to develop an effective treatment have been challenged by the lack of understanding of the pathological mechanisms underlying neurodegeneration. We have shown that Miro1, an outer mitochondrial membrane protein, situates at the intersection of the complex genetic and functional network of PD. Removing Miro1 from the surface of damaged mitochondria is a prerequisite for mitochondrial clearance via mitophagy...
July 25, 2020: Movement Disorders: Official Journal of the Movement Disorder Society
Badrah Saeed Alghamdi, Hanin Abdulbaset AboTaleb
Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Melatonin can diffuse through the blood-brain barrier and has well-known antioxidant and anti-inflammatory properties with almost no side effects; it is, therefore, a promising neuroprotective supplement for many neurological diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, and fibromyalgia...
June 30, 2020: Journal of Integrative Neuroscience
Tiago Barros Silva, Fernanda Borges, Maria Paula Serrão, Patrício Soares-da-Silva
Catechol O-methyltransferase (COMT) inhibitors are valuable co-adjuvant drugs in the clinical management of Parkinson's disease (PD), and recent data also suggest therapeutic benefits in other neurological disorders associated with dopamine depletion. However, the relationship between tolcapone administration with fatal cases of drug-induced liver damage gave COMT inhibitors a bad reputation as hepatotoxic drugs. Thus, there is a pressing need to feed the pipeline with safe COMT inhibitors to replace tolcapone, the only currently available COMT inhibitor that effectively reaches the brain...
July 17, 2020: Drug Discovery Today
Zoltán Orgován, György G Ferenczy, György M Keseru
Metabotropic glutamate receptors (mGlu) are class C G protein-coupled receptors and contain eight subtypes that are omnipresently expressed in the central nervous system. mGlus have relevance in several psychiatric and neurological disorders, therefore mGlus raised considerable interest as drug targets. Drug discovery programs mainly aimed to develop allosteric modulators targeting different mGlus that offer advantages over orthosteric ligands owing to their increased potential to achieve subtype selectivity that prompted discovery programs with a large number of allosteric mGlu ligands reported...
July 19, 2020: ChemMedChem
Emely Pimentel, Kalaiselvi Sivalingam, Mayur Doke, Thangavel Samikkannu
The use of psychostimulants and alcohol disrupts blood-brain barrier (BBB) integrity, resulting in alterations to cellular function, and contributes to neurotoxicity. The BBB is the critical boundary of the central nervous system (CNS) where it maintains intracellular homeostasis and facilitates communication with the peripheral circulation. The BBB is regulated by tight junction (TJ) proteins that closely interact with endothelial cells (EC). The complex TJ protein network consists of transmembrane proteins, including claudins, occludins, and junction adhesion molecules (JAM), as well as cytoskeleton connected scaffolding proteins, zonula occludentes (ZO-1, 2, and 3)...
2020: Frontiers in Neuroscience
Jiao Guo, Xiaoying Jia, Yang Liu, Shaobo Wang, Junyuan Cao, Bo Zhang, Gengfu Xiao, Wei Wang
Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, also leading to fetal intrauterine growth restriction and microcephaly during pregnancy. However, there are currently no approved vaccines or specific antiviral drugs for preventing or treating ZIKV infection. Here, we show that two FDA-approved Na+ /K+ -ATPase inhibitors, ouabain and digoxin, can block ZIKV infection at the replication stage by targeting Na+ /K+ -ATPase...
July 15, 2020: Communications Biology
Yuki Yoshimatsu, Kazunori Tobino, Yuki Ko, Mina Yasuda, Hiromi Ide, Yoshitaka Oku
AIM: The majority of pneumonia in the elderly is attributed to aspiration. Identifying the cause of aspiration is essential for efficient treatment and prevention. However, the methodology on how to investigate the causes is not established. Therefore, we studied cases that were initially admitted for pneumonia and were newly diagnosed with an underlying cause of aspiration. This is the first study to analyze such cases collectively. METHODS: This was a retrospective study...
July 6, 2020: Geriatrics & Gerontology International
Juliana Castro E Silva, Lucianna Lopes do Couto, Henrique de Oliveira Amaral, Flávia Maria Medeiros Gomes, Gabriel Avohay Alves Campos, Luciano Paulino Silva, Márcia Renata Mortari
Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, as also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters...
June 23, 2020: Biochemical Pharmacology
Ariel Nir, Boaz Barak
Myelin is the electrical insulator surrounding the neuronal axon that makes up the white matter (WM) of the brain. It helps increase axonal conduction velocity (CV) by inducing saltatory conduction. Damage to the myelin sheath and WM is associated with many neurological and psychiatric disorders. Decreasing myelin deficits, and thus improving axonal conduction, has the potential to serve as a therapeutic mechanism for reducing the severity of some of these disorders. Myelin deficits have been previously linked to abnormalities in social behavior, suggesting an interplay between brain connectivity and sociability...
June 26, 2020: Glia
Agnieszka Gunia-Krzyżak, Ewa Żesławska, Karolina Słoczyńska, Dorota Żelaszczyk, Aleksandra Sowa, Paulina Koczurkiewicz-Adamczyk, Justyna Popiół, Wojciech Nitek, Elżbieta Pękala, Henryk Marona
Epilepsy is one of the most frequent neurological disorders affecting about 1% of the world's human population. Despite availability of multiple treatment options including antiseizure drugs, it is estimated that about 30% of seizures still remain resistant to pharmacotherapy. Searching for new antiseizure and antiepileptic agents constitutes an important issue within modern medicinal chemistry. Cinnamamide derivatives were identified in preclinical as well as clinical studies as important drug candidates for the treatment of epilepsy...
June 19, 2020: International Journal of Molecular Sciences
Jihyun Park, Kyung Mi Jang, Kwan-Kyu Park
Neuroinflammation plays a vital role in neurodegenerative conditions. Microglia are a key component of the neuroinflammatory response. There is a growing interest in developing drugs to target microglia and thereby control neuroinflammatory processes. Apamin (APM) is a specifically selective antagonist of small conductance calcium-activated potassium (SK) channels. However, its effect on neuroinflammation is largely unknown. We examine the effects of APM on lipopolysaccharide (LPS)-stimulated BV2 and rat primary microglial cells...
June 17, 2020: International Journal of Molecular Sciences
Goodwell Nzou, Robert T Wicks, Nicole R VanOstrand, Gehad A Mekky, Stephanie A Seale, Aya El-Taibany, Elizabeth E Wicks, Carl M Nechtman, Eric J Marotte, Vishruti S Makani, Sean V Murphy, M C Seeds, John D Jackson, Anthony J Atala
The blood-brain barrier (BBB) is a dynamic component of the brain-vascular interface that maintains brain homeostasis and regulates solute permeability into brain tissue. The expression of tight junction proteins between adjacent endothelial cells and the presence of efflux proteins prevents entry of foreign substances into the brain parenchyma. BBB dysfunction, however, is evident in many neurological disorders including ischemic stroke, trauma, and chronic neurodegenerative diseases. Currently, major contributors to BBB dysfunction are not well understood...
June 17, 2020: Scientific Reports
Yuhyun Lee, Kyeong Jae Lee, Jae-Won Jang, Sang-Im Lee, Sohee Kim
Zebrafish has been widely used as an experimental animal in many biological processes to study brain functions, neurological disorders and drug toxicity. Electroencephalogram (EEG), which directly measures brain activities, has been used to diagnose and study neurological disorders. Previous studies have recorded EEG signals from adult zebrafish, but the recordings have been only possible from a single individual. In this study, we developed a system to record EEG of multiple adult zebrafish simultaneously...
September 15, 2020: Biosensors & Bioelectronics
Silvia Rea, David Della-Morte, Francesca Pacifici, Barbara Capuani, Donatella Pastore, Andrea Coppola, Roberto Arriga, Aikaterini Andreadi, Giulia Donadel, Nicola Di Daniele, Alfonso Bellia, Davide Lauro
Patients with diabetes mellitus (DM) are more prone to develop cognitive decline and neurodegenerative diseases. A pathological association between an autosomal dominant neurological disorder caused by brain accumulation in mutated huntingtin (mHTT), known as Huntington disease (HD), and DM, has been reported. By using a diabetic mouse model, we previously suggested a central role of the metabolic pathways of HTT, further suggesting the relevance of this protein in the pathology of DM. Furthermore, it has also been reported that intranasal insulin (Ins) administration improved cognitive function in patients with neurodegenerative disorders such as Alzheimer disease, and that exendin-4 (Ex-4) enhanced lifespan and ameliorated glucose homeostasis in a mouse model of HD...
2020: Frontiers in Pharmacology
Gabriel S Stephens, Chia-Hsuan Fu, Corey P St Romain, Yi Zheng, Justin J Botterill, Helen E Scharfman, Yin Liu, Jeannie Chin
Seizure incidence is increased in Alzheimer's disease (AD) patients and mouse models, and treatment with the antiseizure drug levetiracetam improves cognition. We reported that one mechanism by which seizures can exert persistent effects on cognition is through accumulation of ΔFosB, a transcription factor with a long half-life. Even the infrequent seizures that spontaneously occur in transgenic mice expressing human amyloid precursor protein (APP) lead to persistent increases in ΔFosB in the hippocampus, similar to what we observed in patients with AD or temporal lobe epilepsy...
2020: Frontiers in Neuroscience
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