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https://www.readbyqxmd.com/read/28918129/where-do-substrates-of-diacylglycerol-kinases-come-from-diacylglycerol-kinases-utilize-diacylglycerol-species-supplied-from-phosphatidylinositol-turnover-independent-pathways
#1
REVIEW
Fumio Sakane, Satoru Mizuno, Daisuke Takahashi, Hiromichi Sakai
Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Mammalian DGK comprises ten isozymes (α-κ) and regulates a wide variety of physiological and pathological events, such as cancer, type II diabetes, neuronal disorders and immune responses. DG and PA consist of various molecular species that have different acyl chains at the sn-1 and sn-2 positions, and consequently, mammalian cells contain at least 50 structurally distinct DG/PA species. Because DGK is one of the components of phosphatidylinositol (PI) turnover, the generally accepted dogma is that all DGK isozymes utilize 18:0/20:4-DG derived from PI turnover...
September 9, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28918091/opposed-effects-of-dityrosine-formation-in-soluble-and-aggregated-%C3%AE-synuclein-on-fibril-growth
#2
Michael M Wördehoff, Hamed Shaykhalishahi, Luca Groß, Lothar Gremer, Matthias Stoldt, Alexander K Buell, Dieter Willbold, Wolfgang Hoyer
Parkinson's disease (PD) is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY)-crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from PD patients. Here we report that α-syn is highly susceptible to UV-induced DiY formation...
September 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28918051/lrrk2-antisense-oligonucleotides-ameliorate-%C3%AE-synuclein-inclusion-formation-in-a-parkinson-s-disease-mouse-model
#3
Hien Tran Zhao, Neena John, Vedad Delic, Karli Ikeda-Lee, Aneeza Kim, Andreas Weihofen, Eric E Swayze, Holly B Kordasiewicz, Andrew B West, Laura A Volpicelli-Daley
No treatments exist to slow or halt Parkinson's disease (PD) progression; however, inhibition of leucine-rich repeat kinase 2 (LRRK2) activity represents one of the most promising therapeutic strategies. Genetic ablation and pharmacological LRRK2 inhibition have demonstrated promise in blocking α-synuclein (α-syn) pathology. However, LRRK2 kinase inhibitors may reduce LRRK2 activity in several tissues and induce systemic phenotypes in the kidney and lung that are undesirable. Here, we test whether antisense oligonucleotides (ASOs) provide an alternative therapeutic strategy, as they can be restricted to the CNS and provide a stable, long-lasting reduction of protein throughout the brain...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917980/absence-of-association-of-the-ala58val-rs17571-ctsd-gene-variant-with-parkinson-s-disease-or-amyotrophic-lateral-sclerosis-in-a-han-chinese-population
#4
Jing Xi, Xinglong Yang, Quanzhen Zhao, Jinhua Zheng, Ran An, Sijia Tian, Hongyan Huang, Pingping Ning, Yanming Xu
Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are neurodegenerative diseases that may share genetic risk factors. The exon variant Aal58Val (rs17571) in CTSD was recently associated with AD, leading us to examine whether it also affects risk of ALS and PD. The rs17571 variant was genotyped using the ligase detection reaction in 569 Han Chinese patients with PD, 301 patients with ALS, and healthy controls age- and gender-matched to each patient group. The frequencies of genotypes and alleles were similar between each disease group and its respective control group...
September 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917942/in-vivo-and-in-vitro-testing-of-native-%C3%AE-conotoxins-from-the-injected-venom-of-conus-purpurascens
#5
REVIEW
Mickelene F Hoggard, Alena M Rodriguez, Herminsul Cano, Evan Clark, Han-Shen Tae, David J Adams, Tanja A Godenschwege, Frank Marí
α-Conotoxins inhibit nicotinic acetylcholine receptors (nAChRs) and are used as probes to study cholinergic pathways in vertebrates. Model organisms, such as Drosophila melanogaster, express nAChRs in their CNS that are suitable to investigate the neuropharmacology of α-conotoxins in vivo. Here we report the paired nanoinjection of native α-conotoxin PIA and two novel α-conotoxins, PIC and PIC[O7], from the injected venom of Conus purpurascens and electrophysiological recordings of their effects on the giant fiber system (GFS) of D...
September 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28917824/parkinson-s-disease-susceptibility-variants-and-severity-of-lewy-body-pathology
#6
Michael G Heckman, Koji Kasanuki, Nancy N Diehl, Shunsuke Koga, Alexandra Soto, Melissa E Murray, Dennis W Dickson, Owen A Ross
INTRODUCTION: Meta-analyses of genome-wide association studies (GWAS) have established common genetic risk factors for clinical Parkinson's disease (PD); however, associations between these risk factors and quantitative neuropathologic markers of disease severity have not been well-studied. This study evaluated associations of nominated variants from the most recent PD GWAS meta-analysis with Lewy body disease (LBD) subtype (brainstem, transitional, or diffuse) and pathologic burden of LB pathology as measured by LB counts in five cortical regions in a series of LBD cases...
September 11, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28917552/crispr-correction-of-the-prkag2-gene-mutation-in-the-patient-s-ipsc-derived-cardiomyocytes-eliminates-the-electrophysiological-and-structural-abnormalities
#7
Ronen Ben Jehuda, Binyamin Eisen, Yuval Shemer, Lucy N Mekies, Agnes Szantai, Irina Reiter, Huanhuan Cui, Kaomei Guan, Shiraz Haron-Khun, Dov Freimark, Silke R Sperling, Mihaela Gherghiceanu, Michael Arad, Ofer Binah
BACKGROUND: Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate-kinase (AMPK) cause hypertrophic cardiomyopathy (HCM) and familial-Wolff-Parkinson-White syndrome (WPW). Patients carrying the R302Q mutation in PRKAG2 present sinus bradycardia, escape rhythms, ventricular pre-excitation, supraventricular tachycardia and atrioventricular block. This mutation affects AMPK activity and increases glycogen storage in cardiomyocytes. The link between glycogen storage, WPW, HCM and arrhythmias remains unknown...
September 13, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28917524/tremor-dominant-kyoto-trdk-rats-carry-a-missense-mutation-in-the-gene-encoding-the-sk2-subunit-of-small-conductance-ca-2-activated-k-channel
#8
Takashi Kuramoto, Mayuko Yokoe, Naofumi Kunisawa, Kana Ohashi, Takahito Miyake, Yuki Higuchi, Kazuto Yoshimi, Tomoji Mashimo, Miyuu Tanaka, Mitusru Kuwamura, Shuji Kaneko, Saki Shimizu, Tadao Serikawa, Yukihiro Ohno
Tremor dominant Kyoto (Trdk) is an autosomal dominant mutation that appeared in F344/NSlc rats mutagenized with N-ethyl-N-nitrosourea (ENU). In this study, we characterized and genetically analyzed F344-Trdk/+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344-Trdk/+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson's disease-related tremor, indicating that the pharmacological phenotype of F344-Trdk/+ rats was similar to human ET...
September 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28917506/the-plasmalogen-precursor-analog-ppi-1011-reduces-the-development-of-l-dopa-induced-dyskinesias-in-de-novo-mptp-monkeys
#9
Mélanie Bourque, Laurent Grégoire, Thérèse Di Paolo
The gold standard therapy for Parkinson's disease (PD), L-3,4-dihydroxyphenylalanine (L-DOPA), induces dyskinesias in the majority of patients after years of treatment. Ethanolamine plasmalogens (PlsEtn) play critical roles in membrane structure mediated functions and as a storage depot of polyunsaturated fatty acids such as docosahexaenoic acid. We previously showed that a PlsEtn precursor PPI-1011 reduced already established L-DOPA-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkeys as a PD model...
September 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28917380/the-neuropsychological-profile-of-othello-syndrome-in-parkinson-s-disease
#10
Jennifer A Foley, Thomas T Warner, Lisa Cipolotti
No abstract text is available yet for this article.
August 16, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28917379/effectiveness-and-safety-of-acupuncture-in-the-treatment-of-parkinson-s-disease-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#11
REVIEW
Hyeonseok Noh, Seungwon Kwon, Seung-Yeon Cho, Woo-Sang Jung, Sang-Kwan Moon, Jung-Mi Park, Chang-Nam Ko, Seong-Uk Park
OBJECTIVE: This study aimed to examine the effectiveness and safety of acupuncture in the treatment of Parkinson's disease (PD). METHODS: English, Chinese, and Korean electronic databases were searched up to June 2016. Randomized controlled trials (RCTs) were eligible. The methodological quality was assessed using Cochrane's risk of bias tool. Meta-analysis was performed using RevMan 5.3. RESULTS: In total, 42 studies involving 2625 participants were systematically reviewed...
October 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/28917359/dance-is-more-than-therapy-qualitative-analysis-on-therapeutic-dancing-classes-for-parkinson-s
#12
Priscila A Rocha, Susan C Slade, Jodie McClelland, Meg E Morris
OBJECTIVES: To understand the benefits and limitations of therapeutic dancing classes for people with Parkinson's disease (PD) and how best to design and implement classes. DESIGN: A stakeholder forum explored the opinions of 18 allied health clinicians, dance instructors, people with PD and caregivers. Data were thematically analysed and interpreted within a grounded theory framework. RESULTS: Four main themes were identified: (1) the need to consider the stage of disease progression when designing classes; (2) recognition that dance is more than just therapy; (3) the benefits of carefully selecting music to move by; (4) ways to design classes that are both feasible and engaging...
October 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/28917260/roles-of-sigma-1-receptors-on-mitochondrial-functions-relevant-to-neurodegenerative-diseases
#13
REVIEW
Tzu-Yu Weng, Shang-Yi Anne Tsai, Tsung-Ping Su
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca(2+) signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca(2+) transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense...
September 16, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28916820/accumulation-of-minor-alleles-and-risk-prediction-in-schizophrenia
#14
Pei He, Xiaoyun Lei, Dejian Yuan, Zuobin Zhu, Shi Huang
Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. Accumulation of common polygenic variations has been found to be an important risk factor. Recent studies showed a role for the enrichment of minor alleles (MAs) of SNPs in complex diseases such as Parkinson's disease. Here we similarly studied the role of genome wide MAs in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher average values in minor allele content (MAC) or the average amount of MAs per subject...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916627/interactions-between-medial-prefrontal-cortex-and-dorsomedial-striatum-are-necessary-for-odor-span-capacity-in-rats-role-of-glun2b-containing-nmda-receptors
#15
Don A Davies, Quentin Greba, Jantz C Selk, Jillian K Catton, Landon D Baillie, Sean J Mulligan, John G Howland
Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the involvement of medial prefrontal cortex (mPFC) and dorsal striatum (STR) in the odor span task (OST), a task proposed to assay working memory capacity in rodents. Initially, Long Evans rats were trained to dig in scented sand for food following a serial delayed nonmatching-to-sample rule...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916538/analysis-of-blood-based-gene-expression-in-idiopathic-parkinson-disease
#16
Ron Shamir, Christine Klein, David Amar, Eva-Juliane Vollstedt, Michael Bonin, Marija Usenovic, Yvette C Wong, Ales Maver, Sven Poths, Hershel Safer, Jean-Christophe Corvol, Suzanne Lesage, Ofer Lavi, Günther Deuschl, Gregor Kuhlenbaeumer, Heike Pawlack, Igor Ulitsky, Meike Kasten, Olaf Riess, Alexis Brice, Borut Peterlin, Dimitri Krainc
OBJECTIVE: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). METHODS: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28916501/awakenings-in-rats-by-ultrasounds-a-new-animal-model-for-paradoxical-kinesia
#17
Luan Castro Tonelli, Markus Wöhr, Rainer Schwarting, Liana Melo-Thomas
Paradoxical kinesia refers to a sudden transient ability of akinetic patients to perform motor tasks they are otherwise unable to perform. The mechanisms underlying this phenomenon are unknown due a paucity of valid animal models that faithfully reproduce paradoxical kinesia. Here, in a first experiment, we present a new method to study paradoxical kinesia by "awakening" cataleptic rats through presenting appetitive 50-kHz ultrasonic vocalizations (USV), which are typical for social situations with positive valence, like juvenile play or sexual encounters ("rat laughter")...
September 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28915672/an-updated-meta-analysis-of-amantadine-for-treating-dyskinesia-in-parkinson-s-disease
#18
Min Kong, Maowen Ba, Chao Ren, Ling Yu, Shengjie Dong, Guoping Yu, Hui Liang
In recent years, a few of randomized controlled trials (RCTs) about amantadine for treating dyskinesia in Parkinson's disease (PD) were completed. Here, we conducted a systematic literature review about the clinical research to provide the updated evidence for treating dyskinesia. Electronic search of Medline, PubMed, Cochrane Library, and other databases up to May 2016 for relevant studies was performed. We selected the Unified Parkinson's Disease Rating Scale IV (UPDRS IV) and Dyskinesia Rating Scales (DRS) as efficacy outcomes of amantadine on dyskinesia...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914888/parkinson-disease-asthma-drug-could-protect-against-pd
#19
Charlotte Ridler
No abstract text is available yet for this article.
September 15, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28914884/parkinson-disease-csmd1-gene-mutations-can-lead-to-familial-parkinson-disease
#20
Mitesh Patel
No abstract text is available yet for this article.
September 15, 2017: Nature Reviews. Neurology
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