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https://www.readbyqxmd.com/read/28203480/a-novel-immunosuppressor-5r-5-hydroxytriptolide-alleviates-movement-disorder-and-neuroinflammation-in-a-6-ohda-hemiparkinsonian-rat-model
#1
Ruijun Su, Min Sun, Wei Wang, Jianliang Zhang, Li Zhang, Junli Zhen, Yanjing Qian, Yan Zheng, Xiaomin Wang
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. Promising therapies for PD still need to be explored. Immune dysfunction has been found to be involved in PD pathogenesis. Here, a novel immunosuppressor, (5R)-5-hydroxytriptolide (LLDT8), was used to treat 6-hydroxydopamine (6-OHDA)-induced hemiparkinson rats. We found that oral administration of LLDT8 significantly alleviated apomorphine-induced rotations at a dose of 125 µg/kg, and improved performance in cylinder and rotarod tests at a lower dose of 31...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28168008/protective-effect-of-antioxidants-on-neuronal-dysfunction-and-plasticity-in-huntington-s-disease
#2
REVIEW
Thirunavukkarasu Velusamy, Archana S Panneerselvam, Meera Purushottam, Muthuswamy Anusuyadevi, Pramod Kumar Pal, Sanjeev Jain, Musthafa Mohamed Essa, Gilles J Guillemin, Mahesh Kandasamy
Huntington's disease (HD) is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28144037/automated-analysis-of-connected-speech-reveals-early-biomarkers-of-parkinson-s-disease-in-patients-with-rapid-eye-movement-sleep-behaviour-disorder
#3
Jan Hlavnička, Roman Čmejla, Tereza Tykalová, Karel Šonka, Evžen Růžička, Jan Rusz
For generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson's disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116784/management-of-sleep-disorders-in-parkinson-s-disease-and-multiple-system-atrophy
#4
REVIEW
Aleksandar Videnovic
Parkinson's disease (PD) and multiple system atrophy (MSA) are disorders associated with α synuclein-related neurodegeneration. Nonmotor symptoms are common hallmarks of these disorders, and disturbances of the sleep-wake cycle are among the most common nonmotor symptoms. It is only recently that sleep disturbances have received the attention of the medical and research community. Significant progress has been made in understanding the pathophysiology of sleep and wake disruption in alphasynucleinopathies during the past few decades...
January 24, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28063152/dysfunction-of-central-control-of-breathing-in-amyotrophic-lateral-sclerosis
#5
Bradley N Howell, Daniel S Newman
Dysfunction in central control of breathing in some amyotrophic lateral sclerosis (ALS) patients is not adequately detected with standard evaluation for respiratory dysfunction. Nocturnal oximetry reveals periodic desaturations despite normal respiratory muscle movements. Continuous diaphragmatic electromyography has provided in vivo data consistent with impaired central control of diaphragm motor units. Current understanding of central control of breathing identifies the pre-Botzinger complex as the inspiratory rhythm generator...
January 7, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28055131/subthalamic-nuclei-stimulation-in-patients-with-pantothenate-kinase-associated-neurodegeneration-pkan
#6
Ziyuan Liu, Yang Liu, Yingmai Yang, Lin Wang, Wanchen Dou, Jinzhu Guo, Yu Wang, Yi Guo, Xinhua Wan, Wenbin Ma, Renzhi Wang
INTRODUCTION: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disease that leads to extrapyramidal symptoms, such as dystonia, ataxia, dysarthria, and involuntary movements. Treatment of PKAN with deep brain stimulation (DBS) has been reported, but mainly focuses on targeting the globus pallidus internus (GPi). Subthalamic nuclei (STN) may also be a potential target for treatment of PKAN. METHODS: In this study, we reviewed three patients with PKAN (two with typical PKAN and one with atypical PKAN) treated by bilateral STN stimulation and present a review of the literature...
January 5, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28053030/tau-isoforms-imbalance-impairs-the-axonal-transport-of-the-amyloid-precursor-protein-in-human-neurons
#7
Valentina Lacovich, Sonia L Espindola, Matías Alloatti, Victorio Pozo Devoto, Lucas E Cromberg, Mária E Čarná, Giancarlo Forte, Jean-Marc Gallo, Luciana Bruno, Gorazd B Stokin, M Elena Avale, Tomás L Falzone
: Tau, as a microtubule (MT)-associated protein, participates in key neuronal functions such as the regulation of MT dynamics, axonal transport, and neurite outgrowth. Alternative splicing of exon 10 in the tau primary transcript gives rise to protein isoforms with three (3R) or four (4R) MT binding repeats. Although tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated with the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28010125/proposed-association-between-the-hexanucleotide-repeat-of-c9orf72-and-opposability-index-of-the-thumb
#8
Zhongbo Chen, Kuang Lin, Jeffrey D Macklis, Ammar Al-Chalabi
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by motor neuron and sub-cerebral projection neuron degeneration. We sought to explore the particular susceptibility of humans to neurodegeneration and whether any characteristic human features might predispose to selective vulnerability of the critical motor circuitry in ALS. The pathophysiology of the C9orf72 repeat is not yet understood, despite its role as a common cause of ALS and frontotemporal dementia. METHODS: We examined the development of the monosynaptic cortico-motoneuronal system, key to skilled hand movements, measured by the thumb opposability index, and its relationship to the C9orf72 hexanucleotide repeat expansion, a strong predisposing factor for neurodegeneration, using the genomic tool BLAST...
December 23, 2016: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28004338/network-analysis-identifies-disease-specific-pathways-for-parkinson-s-disease
#9
Chiara Monti, Ilaria Colugnat, Leonardo Lopiano, Adriano Chiò, Tiziana Alberio
Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis...
December 21, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27940361/nurr1-overexpression-exerts-neuroprotective-and-anti-inflammatory-roles-via-down-regulating-ccl2-expression-in-both-in%C3%A2-vivo-and-in%C3%A2-vitro-parkinson-s-disease-models
#10
Wei Liu, Yang Gao, Na Chang
The abnormality of nuclear receptor-related protein 1 (Nurr1) in expression and function can contribute to neurodegeneration of dopaminergic neurons and occurrence of Parkinson's disease (PD). However, its related mechanism in PD is still unknown. In this study, we found that Nurr1 was down-regulated and CCL2 was up-regulated in PD patients and PD mice. CCL2 promoted apoptosis and secretion of TNF-α and IL-1β in SH-SY5Y cells and inhibited cell viability while knockdown of CCL2 exerted the opposite effects...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27886407/first-in-human-assessment-of-prx002-an-anti-%C3%AE-synuclein-monoclonal-antibody-in-healthy-volunteers
#11
Dale B Schenk, Martin Koller, Daniel K Ness, Sue G Griffith, Michael Grundman, Wagner Zago, Jay Soto, George Atiee, Susanne Ostrowitzki, Gene G Kinney
BACKGROUND: α-Synuclein is a major component of pathologic inclusions that characterize Parkinson's disease. PRX002 is an antibody that targets α-synuclein, and its murine parent antibody 9E4 has been shown in preclinical studies to reduce α-synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration in human α-synuclein transgenic mice. METHODS: This first-in-human, randomized, double-blind, placebo-controlled, phase 1 study assessed the impact of PRX002 administered to 40 healthy participants in 5 ascending-dose cohorts (n = 8/cohort) in which participants were randomly assigned to receive a single intravenous infusion of study drug (0...
November 25, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27884168/ataxia-telangiectasia-a-review
#12
REVIEW
Cynthia Rothblum-Oviatt, Jennifer Wright, Maureen A Lefton-Greif, Sharon A McGrath-Morrow, Thomas O Crawford, Howard M Lederman
DEFINITION OF THE DISEASE: Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome. EPIDEMIOLOGY: The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births. CLINICAL DESCRIPTION: A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages...
November 25, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27862279/pet-and-mri-detection-of-early-and-progressive-neurodegeneration-in-spinocerebellar-ataxia-type-36
#13
Pablo Aguiar, Julio Pardo, Manuel Arias, Beatriz Quintáns, Montse Fernández-Prieto, Rocío Martínez-Regueiro, José-Manuel Pumar, Jesús Silva-Rodríguez, Álvaro Ruibal, María-Jesús Sobrido, Julia Cortés
BACKGROUND: The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans. METHODS: Twenty SCA36 patients underwent a study consisting of FDG-PET and MRI scans...
November 10, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27837099/tau-isoforms-imbalance-impairs-the-axonal-transport-of-the-amyloid-precursor-protein-in-human-neurons
#14
Valentina Lacovich, Sonia L Espindola, Matías Alloatti, Victorio Pozo Devoto, Lucas Cromberg, Mária Čarná, Giancarlo Forte, Jean-Marc Gallo, Luciana Bruno, Gorazd B Stokin, M Elena Avale, Tomás L Falzone
: Tau, as a microtubule-associated protein, participates in key neuronal functions such as the regulation of microtubule dynamics, axonal transport and neurite outgrowth. Alternative splicing of exon 10 in the tau primary transcript gives rise to protein isoforms with three (3R) or four (4R) microtubule binding repeats. While tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated to the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive...
November 11, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27829351/recent-updates-in-imperative-natural-compounds-for-healthy-brain-and-nerve-function-a-systematic-review-of-implications-for-multiple-sclerosis
#15
Nima Sanadgol, Shahram Shahraki Zahedani, Mohammad Sharifzadeh, Roghayeh Khalseh, Gullam Reza Barbari, Mohammad Abdollahi
BACKGROUND: The evolution of the 'Green' movement in western society has changed attitudes in the general population who now perceive natural compounds as being inherently harmless and more desirable than artificial chemical products. OBJECTIVE: Considering the growing interest towards introducing naturally emerged medicines, the purpose of this review was to overview the ongoing research into prevention and treatment of multiple sclerosis (MS) lesions. METHOD: This review was carried out by searching bibliographic databases such as PubMed and Scopus for studies reported between 1th January 2008 to 30rd January 2016 on MS patients or animal models of MS, investigating the beneficial effects of natural compounds in MS treatment...
November 8, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27787934/intake-of-antioxidant-vitamins-and-risk-of-parkinson-s-disease
#16
Katherine C Hughes, Xiang Gao, Iris Y Kim, Eric B Rimm, Molin Wang, Marc G Weisskopf, Michael A Schwarzschild, Alberto Ascherio
INTRODUCTION: Oxidative stress is proposed to be one of the potential mechanisms leading to neurodegeneration in Parkinson's disease. However, previous epidemiologic studies investigating associations between antioxidant vitamins, such as vitamins E and C and carotenoids, and PD risk have produced inconsistent results. OBJECTIVE: The objective of this work was to prospectively examine associations between intakes of antioxidant vitamins, including vitamins E and C and carotenoids, and PD risk...
December 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27776205/investigations-on-16-arylideno-steroids-as-a-new-class-of-neuroprotective-agents-for-the-treatment-of-alzheimer-s-and-parkinson-s-diseases
#17
Ranjit Singh, Ranju Bansal
Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute to neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27773637/human-sirtuins-structures-and-flexibility
#18
REVIEW
Lionel Sacconnay, Pierre-Alain Carrupt, Alessandra Nurisso
In recent years, sirtuins (SIRTs), members of histone deacetylases (HDACs) class III, have been found to modulate cellular processes related to the development of human aging-related pathologies (i.e. cancer, neurodegeneration, metabolic disorders). Several crystallographic structures and computational studies have shed light into their catalytic mechanism of action, identifying also the structural elements for the design of selective drug candidates. In this review, we first aim at summarizing the structural features characterizing human SIRTs...
December 2016: Journal of Structural Biology
https://www.readbyqxmd.com/read/27720640/endophilin-a-deficiency-induces-the-foxo3a-fbxo32-network-in-the-brain-and-causes-dysregulation-of-autophagy-and-the-ubiquitin-proteasome-system
#19
John D Murdoch, Christine M Rostosky, Sindhuja Gowrisankaran, Amandeep S Arora, Sandra-Fausia Soukup, Ramon Vidal, Vincenzo Capece, Siona Freytag, Andre Fischer, Patrik Verstreken, Stefan Bonn, Nuno Raimundo, Ira Milosevic
Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27639641/energy-defects-in-huntington-s-disease-why-in%C3%A2-vivo-evidence-matters
#20
REVIEW
Géraldine Liot, Julien Valette, Jérémy Pépin, Julien Flament, Emmanuel Brouillet
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder associated with involuntary abnormal movements (chorea), cognitive deficits and psychiatric disturbances. The most striking neuropathological change in HD is the early atrophy of the striatum. While the disease progresses, other brain structures also degenerate, including the cerebral cortex. Changes are also seen outside the brain, in particular weight loss/cachexia despite high dietary intake. The disease is caused by an abnormal expansion of a CAG repeat in the gene encoding the huntingtin protein (Htt)...
February 19, 2017: Biochemical and Biophysical Research Communications
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