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Parkinson’s disease

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https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#1
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926857/a-lon-clpp-proteolytic-axis-degrades-complex-i-to-extinguish-ros-production-in-depolarized-mitochondria
#2
Kenneth Robert Pryde, Jan Willem Taanman, Anthony Henry Schapira
Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson's disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926449/the-role-of-dopamine-in-the-pathophysiology-and-treatment-of-apathy
#3
T T-J Chong, M Husain
Disorders of diminished motivation, such as apathy, are common and prevalent across a wide range of medical conditions, including Parkinson's disease, Alzheimer's dementia, stroke, depression, and schizophrenia. Such disorders have a significant impact on morbidity and quality of life, yet their management lacks consensus and remains unsatisfactory. Here, we review laboratory and clinical evidence for the use of dopaminergic therapies in the treatment of apathy. Dopamine is a key neurotransmitter that regulates motivated decision making in humans and other species...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27925292/cognitive-impairment-in-parkinson-s-disease-impact-on-quality-of-life-of-carers
#4
R A Lawson, A J Yarnall, F Johnston, G W Duncan, T K Khoo, D Collerton, J P Taylor, D J Burn
BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers...
December 7, 2016: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/27925204/rabs-membrane-dynamics-and-parkinson-s-disease
#5
REVIEW
Bor Luen Tang
Genes encoding cellular membrane trafficking components, namely RAB7L1 and RAB39B, are more recently recognized factors associated with Parkinson's disease (PD). Encoded by a gene within the PARK16 locus, RAB7L1 interacts with Leucine-rich repeat kinase 2 (LRRK2) to act in intracellular transport processes that are likely important in neuronal survival and function. LRRK2 also directly phosphorylates a number of other Rab proteins. On the other hand, nonsense and missense mutations of the X-chromosome localized RAB39B, were shown to underlie X-linked intellectual disability (ID) in male patients with early-onset PD...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924925/replicatively-senescent-human-fibroblasts-reveal-a-distinct-intracellular-metabolic-profile-with-alterations-in-nad-and-nicotinamide-metabolism
#6
Emma L James, James A E Lane, Ryan D Michalek, Edward D Karoly, E Kenneth Parkinson
Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924721/structural-brain-connectome-and-cognitive-impairment-in-parkinson-disease
#7
Sebastiano Galantucci, Federica Agosta, Elka Stefanova, Silvia Basaia, Martijn P van den Heuvel, Tanja Stojković, Elisa Canu, Iva Stanković, Vladana Spica, Massimiliano Copetti, Delia Gagliardi, Vladimir S Kostić, Massimo Filippi
Purpose To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography...
December 7, 2016: Radiology
https://www.readbyqxmd.com/read/27924069/retrograde-trafficking-of-vmat2-and-its-role-in-protein-stability-in-non-neuronal-cells
#8
Qiuzi Wu, Hongfei Xu, Wei Wang, Fei Chang, Yu Jiang, Yongjian Liu
Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2 (VMAT2) contributes to the pathogenesis of Parkinson's disease. That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases. However, whether VMAT2 function is regulated by retrograde trafficking is unknown. By using biochemistry and cell biology approaches, we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27923670/early-and-progressive-microstructural-brain-changes-in-mice-overexpressing-human-%C3%AE-synuclein-detected-by-diffusion-kurtosis-imaging
#9
Amit Khairnar, Jana Ruda-Kucerova, Nikoletta Szabó, Eva Drazanova, Anas Arab, Birgit Hutter-Paier, Joerg Neddens, Peter Latta, Zenon Starcuk, Irena Rektorova
Diffusion kurtosis imaging (DKI) is sensitive in detecting α-Synuclein (α-Syn) accumulation-associated microstructural changes at late stages of the pathology in α-Syn overexpressing TNWT-61 mice. The aim of this study was to perform DKI in young TNWT-61 mice when α-Syn starts to accumulate and to compare the imaging results with an analysis of motor and memory impairment and α-Syn levels. Three-month-old (3mo) and six-month-old (6mo) mice underwent DKI scanning using the Bruker Avance 9.4 Tesla magnetic resonance imaging system...
December 3, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27923655/development-of-a-novel-catalytic-amyloid-displaying-a-metal-dependent-atpase-like-activity
#10
Octavio Monasterio, Esteban Nova, Rodrigo Diaz-Espinoza
Amyloids are protein aggregates of highly regular structure that are involved in diverse pathologies such as Alzheimer's and Parkinson's disease. Recent evidence has shown that under certain conditions, small peptides can self-assemble into amyloids that exhibit catalytic reactivity towards certain compounds. Here we report a novel peptide with a sequence derived from the active site of RNA polymerase that displays hydrolytic activity towards ATP. The catalytic reaction proceeds in the presence of the divalent metal manganese and the products are ADP and AMP...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27923428/association-of-restless-legs-syndrome-with-incident-parkinson-disease
#11
Della Bro, Ruth O'Hara, Michelle Primeau, Andrea Hanson-Kahn, Joachim Hallmayer, Jonathan A Bernstein
STUDY OBJECTIVES: The association between restless legs syndrome (RLS) and Parkinson's Disease (PD) has been extensively studied with inconclusive results, therefore we prospectively examined the associations of the presence of RLS with development of incident PD. METHODS: From a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60±14 years, 93% male, median follow-up time of 7.8 years (IQR: 6.4-8.4 years)), we created a propensity-matched cohort of 100,882 PD-free patients and examined the association between prevalent RLS and incident PD...
November 28, 2016: Sleep
https://www.readbyqxmd.com/read/27923423/comparison-between-automatic-and-visual-scorings-of-rem-sleep-without-atonia-for-the-diagnosis-of-rem-sleep-behavior-disorder-in-parkinson-disease
#12
Michela Figorilli, Raffaele Ferri, Maurizio Zibetti, Patricia Beudin, Monica Puligheddu, Leonardo Lopiano, Alessandro Cicolin, Frank Durif, Ana Marques, Maria Livia Fantini
STUDY OBJECTIVES: To compare three different methods, two visual and one automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD) in Parkinson's disease (PD) patients. METHODS: Sixty-two consecutive patients with idiopathic PD underwent videopolysomnographic recording and showed more than 5 minutes of REM sleep. The electromyogram (EMG) during REM sleep was analyzed by means of two visual methods (Montréal and SINBAR) and one automatic analysis (REM Atonia Index or RAI)...
November 28, 2016: Sleep
https://www.readbyqxmd.com/read/27922865/additional-value-of-early-phase-18f-fp-cit-pet-image-for-differential-diagnosis-of-atypical-parkinsonism
#13
Soyoung Jin, Minyoung Oh, Seung Jun Oh, Jungsu S Oh, Sang Ju Lee, Sun Ju Chung, Jae Seung Kim
PURPOSE: Regional cerebral perfusion is coupled to metabolism in general. Early perfusion dominant imaging using F-FP-CIT PET (pCIT) may provide complementary information to delayed dopamine transporter dominant images. We investigated the ability of pCIT to differentiate atypical Parkinson disorder from Parkinson disease (PD) compared to FDG and the image quality for optimizing the acquisition time. METHODS: Sixty-seven subjects [PD, 23 subjects; multiple system atrophy-cerebellar type (MSA-C), 27 subjects; MSA-Parkinson type (MSA-P), 12 subjects; and progressive supranuclear palsy (PSP), 5 subjects] underwent F-FP-CIT and FDG PET...
December 3, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27922660/combined-vision-and-wearable-sensors-based-system-for-movement-analysis-in-rehabilitation
#14
Sofija Spasojević, Tihomir V Ilić, Slađan Milanović, Veljko Potkonjak, Aleksandar Rodić, José Santos-Victor
BACKGROUND: Traditional rehabilitation sessions are often a slow, tedious, disempowering and non-motivational process, supported by clinical assessment tools, i.e. evaluation scales that are prone to subjective rating and imprecise interpretation of patient's performance. Poor patient motivation and insufficient accuracy are thus critical factors that can be improved by new sensing / processing technologies. OBJECTIVES: We aim to develop a portable and affordable system, suitable for home rehabilitation, which combines vision-based and wearable sensors...
December 6, 2016: Methods of Information in Medicine
https://www.readbyqxmd.com/read/27921253/aberrant-alterations-of-mitochondrial-factors-drp1-and-opa1-in-the-brains-of-scrapie-experiment-rodents
#15
Xiao -Dong Yang, Qi Shi, Jing Sun, Yan Lv, Yue Ma, Cao Chen, Kang Xiao, Wei Zhou, Xiao-Ping Dong
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27921233/in-vivo-calcium-imaging-and-parkinson-s-disease
#16
Tianwen Huang, Qinyong Ye
No abstract text is available yet for this article.
December 2, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27920671/proceedings-of-the-fourth-annual-deep-brain-stimulation-think-tank-a-review-of-emerging-issues-and-technologies
#17
Wissam Deeb, James J Giordano, Peter J Rossi, Alon Y Mogilner, Aysegul Gunduz, Jack W Judy, Bryan T Klassen, Christopher R Butson, Craig Van Horne, Damiaan Deny, Darin D Dougherty, David Rowell, Greg A Gerhardt, Gwenn S Smith, Francisco A Ponce, Harrison C Walker, Helen M Bronte-Stewart, Helen S Mayberg, Howard J Chizeck, Jean-Philippe Langevin, Jens Volkmann, Jill L Ostrem, Jonathan B Shute, Joohi Jimenez-Shahed, Kelly D Foote, Aparna Wagle Shukla, Marvin A Rossi, Michael Oh, Michael Pourfar, Paul B Rosenberg, Peter A Silburn, Coralie de Hemptine, Philip A Starr, Timothy Denison, Umer Akbar, Warren M Grill, Michael S Okun
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome...
2016: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/27920668/getting-mirna-therapeutics-into-the-target-cells-for-neurodegenerative-diseases-a-mini-review
#18
REVIEW
Ming Ming Wen
miRNAs play important roles in modulating gene expression in varying cellular processes and disease pathogenesis, including neurodegenerative diseases. Several miRNAs are expressed in the brain, control brain development and are identified as important biomarkers in the pathogenesis of motor-and neuro-cognitive diseases such as Alzheimer's (AD), Huntington's and Parkinson's diseases (PD) and amyotrophic lateral sclerosis. These remarkable miRNAs could be used as diagnostic markers and therapeutic targeting potential for many stressful and untreatable progressive neurodegenerative diseases...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27920026/the-transcellular-propagation-and-intracellular-trafficking-of-%C3%AE-synuclein
#19
George K Tofaris, Michel Goedert, Maria Grazia Spillantini
Parkinson's disease is the second most common neurodegenerative disorder, with only partial symptomatic therapy and no mechanism-based therapies. The accumulation and aggregation of α-synuclein is causatively linked to the sporadic form of the disease, which accounts for 95% of cases. The pathology is a result of a gain of toxic function of misfolded α-synuclein conformers, which can template the aggregation of soluble monomers and lead to cellular dysfunction, at least partly by interfering with membrane fusion events at synaptic terminals...
December 5, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27919828/mucuna-pruriens-reduces-inducible-nitric-oxide-synthase-expression-in-parkinsonian-mice-model
#20
Satyndra Kumar Yadav, Sachchida Nand Rai, Surya Pratap Singh
Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp...
December 2, 2016: Journal of Chemical Neuroanatomy
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