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https://www.readbyqxmd.com/read/29223392/parkinson-s-disease-associated-mutant-lrrk2-phosphorylates-rab7l1-and-modifies-trans-golgi-morphology
#1
Tetta Fujimoto, Tomoki Kuwahara, Tomoya Eguchi, Maria Sakurai, Tadayuki Komori, Takeshi Iwatsubo
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the major genetic cause of autosomal-dominantly inherited Parkinson's disease. LRRK2 is implicated in the regulation of intracellular trafficking, neurite outgrowth and PD risk in connection with Rab7L1, a putative interactor of LRRK2. Recently, a subset of Rab GTPases have been reported as substrates of LRRK2. Here we examine the kinase activity of LRRK2 on Rab7L1 in situ in cells. Phos-tag analyses and metabolic labeling assays revealed that LRRK2 readily phosphorylates Golgi-localized wild-type Rab7L1 but not mutant forms that are distributed in the cytoplasm...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29223177/well-being-and-distress-of-patients-with-parkinson-s-disease-a-comparative-investigation
#2
Francesca Vescovelli, Daniele Sarti, Chiara Ruini
BACKGROUND: Psychological resources, such as psychological well-being (PWB) and life satisfaction (LS) can aid individuals suffering from chronic illnesses to cope with their illness. The aim of this study was to investigate PWB, LS, quality of life (QoL), and distress in patients with Parkinson's disease (PD) and to compare them with healthy controls. METHODS: One hundred and thirteen individuals were recruited. Fifty of the participants suffered from PD, while 53 individuals reported other non-neurological diseases...
December 10, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#3
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29223069/neuropsychological-and-clinical-heterogeneity-of-cognitive-impairment-in-patients-with-multiple-system-atrophy
#4
Lorena Broseghini Barcelos, Flávia Saad, Carla Giacominelli, Roberta Arb Saba, Patrícia Maria de Carvalho Aguiar, Sonia Maria Azevedo Silva, Vanderci Borges, Paulo Henrique Ferreira Bertolucci, Henrique Ballalai Ferraz
OBJECTIVE: We evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C). PATIENTS AND METHODS: This cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinson's disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI)...
October 31, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29222936/role-of-central-oxytocin-and-dopamine-systems-in-nociception-and-their-possible-interactions-suggested-hypotheses
#5
Mohammed Gamal-Eltrabily, Alfredo Manzano-García
Central oxytocin and dopamine have an important role in the process of nociception at the spinal level as well as supraspinal structures, e.g. anterior cingulate cortex, insular cortex, amygdala, nucleus accumbens, and hypothalamus. Many studies have pointed out the importance of both systems in the pain descending modulatory system and in pain-related symptoms in some chronic disorders, e.g. Parkinson disease and fibromyalgia. The interaction between oxytocin and dopamine systems has been addressed in some motivational behaviors, e...
December 9, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29222835/effective-network-of-deep-brain-stimulation-of-subthalamic-nucleus-with-bimodal-positron-emission-tomography-functional-magnetic-resonance-imaging-in-parkinson-s-disease
#6
Hui-Min Chen, Zhi-Qiang Sha, Hui-Zi Ma, Yong He, Tao Feng
AIMS: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment strategy for patients with Parkinson's disease. However, the biological mechanism underlying DBS treatment remains poorly understood. METHOD: In this study, we investigated how STN-DBS modulated the brain network using a bimodal positron emission tomography (PET)/functional magnetic resonance imaging (fMRI) dataset. We first performed an activation likelihood estimation meta-analysis of 13 PET/SPECT studies concerning STN-DBS effects on resting-state brain activity in Parkinson's disease...
December 8, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29222776/culture-of-rat-mesencephalic-dopaminergic-neurons-and-application-to-neurotoxic-and-neuroprotective-agents
#7
Stephen D Skaper, Massimo Barbierato, Vanni Ferrari, Morena Zusso, Laura Facci
Dopaminergic neuronal cell degeneration is the principal characteristic feature of the neuropathology of Parkinson disease. Cultures of mesencephalic neurons are widely used as a source of dopaminergic neurons for the study of mechanisms implicated in dopaminergic cell death and for the evaluation of potential dopaminergic neuroprotective agents, including neurotrophic factors. This chapter presents a detailed protocol for the preparation of rat mesencephalic cell cultures and their application to evaluating the effect of the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium and the neuroprotective action of brain-derived neurotrophic factor...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222591/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-current-concepts-and-controversies
#8
REVIEW
Kurt A Jellinger
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD...
December 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29222404/lack-of-parkin-anticipates-the-phenotype-and-affects-mitochondrial-morphology-and-mtdna-levels-in-a-mouse-model-of-parkinson-s-disease
#9
Milena Pinto, Nadee Nissanka, Carlos T Moraes
PARK2 is the most common gene mutated in monogenic recessive familial cases of Parkinson's disease (PD). Pathogenic mutations cause a loss of function of the encoded protein Parkin. ParkinKO mice, however, poorly represent human PD symptoms as they only exhibit mild motor phenotypes, minor dopamine metabolism abnormalities, and no signs of dopaminergic neurodegeneration. Parkin has been shown to participate in mitochondrial turnover, by targeting damaged mitochondria, with low membrane potential, to mitophagy...
December 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29222224/subthalamotomy-for-parkinson-s-disease-clinical-outcome-and-topography-of-lesions
#10
Rafael Rodriguez-Rojas, Maylen Carballo-Barreda, Lazaro Alvarez, Jorge Guridi, Nancy Pavon, Ivan Garcia-Maeso, Raul Macías, Maria C Rodriguez-Oroz, Jose Angel Obeso
OBJECTIVE: Subthalamotomy is an effective alternative for the treatment of Parkinson's disease (PD). However, uncertainty about the optimal target location and the possibility of inducing haemichorea-ballism have limited its application. We assessed the correlation between the topography of radiofrequency-based lesions of the subthalamic nucleus (STN) with motor improvement and the emergence of haemichorea-ballism. METHODS: Sixty-four patients with PD treated with subthalamotomy were evaluated preoperatively and postoperatively using the Unified Parkinson's Disease Rating Scale motor score (UPDRSm), MRI and tractography...
December 8, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29221856/light-triggered-dissociation-of-self-assembled-%C3%AE-amyloid-aggregates-into-small-nontoxic-fragments-by-ruthenium-ii-complex
#11
Giyeong Son, Byung Il Lee, You Jung Chung, Chan Beum Park
The self-assembly of β-amyloid (A β) peptides into highly stable plaques is a major hallmark of Alzheimer's disease. Here, we report visible light-driven dissociation of β -sheet-rich A β aggregates into small, nontoxic fragments using ruthenium (II) complex {[Ru(bpy)3]2+} that functions as a highly sensitive, biocompatible, photoresponsive anti-A β agent. According to our multiple analyses using thioflavin T, bicinchoninic acid, dynamic light scattering, atomic force microscopy, circular dichroism, and Fourier transform infrared spectroscopy, [Ru(bpy)3]2+ successfully disassembled A β aggregates by destabilizing the β -sheet secondary structure under illumination of white light-emitting diode light...
December 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29221831/processing-of-implicit-versus-explicit-predictive-contextual-information-in-parkinson-s-disease
#12
Ling Li, Pablo Diaz-Brage, Helena Fernandez-Lago, Noa Fogelson
We investigated the effects of implicit versus explicit local contextual processing in Parkinson's disease (PD) using electrophysiological measures. EEG recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a predictive sequence signaling the occurrence of a target event. PD patients ("on" medication) and healthy controls performed two sessions: in the first the regularity of the predictive sequence was implicit, while in the second this regularity was made explicit...
December 5, 2017: Neuropsychologia
https://www.readbyqxmd.com/read/29220864/the-nature-of-catecholamine-containing-neurons-in-the-enteric-nervous-system-in-relationship-with-organogenesis-normal-human-anatomy-and-neurodegeneration
#13
G Natale, L Ryskalin, C L Busceti, F Biagioni, F Fornai
The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells...
September 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29220570/neuromicrobiology-how-microbes-influence-the-brain
#14
Cesar de la Fuente-Nunez, Beatriz Torres Meneguetti, Octávio Luiz Franco, Timothy K Lu
We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in health and disease via the activity of the gut-brain axis, possibly contributing to autism spectrum disorders, Alzheimer's disease, Parkinson's disease, depression, and anxiety disorder. Gut microbes may also be involved in nociception, complex host behaviors, and brain development...
December 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29219207/motor-complications-in-parkinson-s-disease-striatal-molecular-and-electrophysiological-mechanisms-of-dyskinesias
#15
REVIEW
Barbara Picconi, Ledia F Hernández, Jose A Obeso, Paolo Calabresi
Long-term levodopa (l-dopa) treatment in patients with Parkinson´s disease (PD) is associated with the development of motor complications (ie, motor fluctuations and dyskinesias). The principal etiopathogenic factors are the degree of nigro-striatal dopaminergic loss and the duration and dose of l-dopa treatment. In this review article we concentrate on analysis of the mechanisms underlying l-dopa-induced dyskinesias, a phenomenon that causes disability in a proportion of patients and that has not benefited from major therapeutic advances...
December 8, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29218916/visage-integrating-external-knowledge-into-electronic-medical-record-visualization
#16
Edward W Huang, Sheng Wang, ChengXiang Zhai
In this paper, we present VisAGE, a method that visualizes electronic medical records (EMRs) in a low-dimensional space. Effective visualization of new patients allows doctors to view similar, previously treated patients and to identify the new patients' disease subtypes, reducing the chance of misdiagnosis. However, EMRs are typically incomplete or fragmented, resulting in patients who are missing many available features being placed near unrelated patients in the visualized space. VisAGE integrates several external data sources to enrich EMR databases to solve this issue...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29218631/intracellular-metal-binding-and-redox-behavior-of-human-dj-1
#17
Letizia Barbieri, Enrico Luchinat, Lucia Banci
DJ-1 is a conserved, ubiquitous protein associated to a large number of intracellular processes. Human DJ-1 has been linked to several pathologies, including hereditary forms of Parkinson's disease, cancer, and amyotrophic lateral sclerosis. Several cytoprotective functions of DJ-1 have been reported, however, its actual mechanisms of action remain elusive. In vitro, DJ-1 has been shown to bind zinc and copper(II) at its active site, which contains a conserved cysteine (C106), and copper(I) at a different binding site...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29218558/sas-based-studies-of-protein-fibrillation
#18
Carlotta Marasini, Bente Vestergaard
Protein fibrillation is associated with a number of fatal amyloid diseases (e.g. Alzheimer's and Parkinson's diseases). From a structural point of view, the aggregation process starts from an ensemble of native states that convert into transiently formed oligomers, higher order assemblies and protofibrils and, finally, fibrils. The different species exist in equilibrium in solution leading to a high degree of sample heterogeneity. It is impossible to physically isolate any single species for structural analysis: separation will alter the equilibrium and potentially cause structural changes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29218504/temporal-spatial-profiling-of-pedunculopontine-galanin-cholinergic-neurons-in-the-lactacystin-rat-model-of-parkinson-s-disease
#19
Joanna L Elson, Rafael Kochaj, Richard Reynolds, Ilse S Pienaar
Parkinson's disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, while being upregulated in degenerating brain regions associated with cognitive decline...
December 7, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29218503/differential-alterations-in-metabolism-and-proteolysis-related-proteins-in-human-parkinson-s-disease-substantia-nigra
#20
Edna Grünblatt, Josefine Ruder, Camelia Maria Monoranu, Peter Riederer, Moussa Bh Youdim, Silvia A Mandel
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found...
December 7, 2017: Neurotoxicity Research
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