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https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#1
REVIEW
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28231468/parkinson-sac-domain-mutation-in-synaptojanin-1-impairs-clathrin-uncoating-at-synapses-and-triggers-dystrophic-changes-in-dopaminergic-axons
#2
Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J McCartney, Heather Wheeler, Eric A Bushong, Daniela Boassa, Mark H Ellisman, Timothy A Ryan, Pietro De Camilli
Synaptojanin 1 (SJ1) is a major presynaptic phosphatase that couples synaptic vesicle endocytosis to the dephosphorylation of PI(4,5)P2, a reaction needed for the shedding of endocytic factors from their membranes. While the role of SJ1's 5-phosphatase module in this process is well recognized, the contribution of its Sac phosphatase domain, whose preferred substrate is PI4P, remains unclear. Recently a homozygous mutation in its Sac domain was identified in early-onset parkinsonism patients. We show that mice carrying this mutation developed neurological manifestations similar to those of human patients...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231462/the-complicated-relationship-between-gaucher-disease-and-parkinsonism-insights-from-a-rare-disease
#3
REVIEW
Elma Aflaki, Wendy Westbroek, Ellen Sidransky
The discovery of a link between mutations in GBA1, encoding the lysosomal enzyme glucocerebrosidase, and the synucleinopathies directly resulted from the clinical recognition of patients with Gaucher disease with parkinsonism. Mutations in GBA1 are now the most common known genetic risk factor for several Lewy body disorders, and an inverse relationship exists between levels of glucocerebrosidase and oligomeric α-synuclein. While the underlying mechanisms are still debated, this complicated association is shedding light on the role of lysosomes in neurodegenerative disorders, demonstrating how insights from a rare disorder can direct research into the pathogenesis and therapy of seemingly unrelated common diseases...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231027/insomnia-sleep-quality-and-quality-of-life-in-mild-to-moderate-parkinson-s-disease
#4
Shirin Shafazand, Douglas M Wallace, Kristopher L Arheart, Silvia Vargas, Corneliu C Luca, Henry Moore, Heather Katzen, Bonnie Levin, Carlos Singer
RATIONALE: Sleep disorders are prevalent in Parkinson's disease and yet under reported in clinical settings. The contribution of sleep disorders to health-related quality of life (HRQOL) for patients with this degenerative neurological disease are not well known. OBJECTIVES: To evaluate the impact of insomnia symptoms, obstructive sleep apnea (OSA), and poor sleep quality on HRQOL in a cohort of patients with idiopathic Parkinson's disease. METHODS: We enrolled a convenience sample of 66 adults seen in the University of Miami Movement Disorders Clinic between July 2011 and June 2013...
February 23, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28230968/inhibition-of-%C3%AE-synuclein-fibril-elongation-by-hsp70-is-governed-by-a-kinetic-binding-competition-between-%C3%AE-synuclein-species
#5
Francesco A Aprile, Paolo Arosio, Giuliana Fusco, Serene W Chen, Janet R Kumita, Anne Dhulesia, Paolo Tortora, Tuomas P J Knowles, Michele Vendruscolo, Christopher M Dobson, Nunilo Cremades
The Hsp70 family of chaperones plays an essential role in suppressing protein aggregation in the cell. Here we investigate the factors controlling the intrinsic ability of human Hsp70 to inhibit the elongation of amyloid fibrils formed by the Parkinson's disease-related protein α-synuclein. Using kinetic analysis, we show that Hsp70 binds preferentially to α-synuclein fibrils as a consequence of variations in the association and dissociation rate constants of binding to the different aggregated states of the protein...
February 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28230630/update-on-the-22q11-2-deletion-syndrome-and-its-relevance-to-schizophrenia
#6
Lily Van, Erik Boot, Anne S Bassett
PURPOSE OF REVIEW: Schizophrenia occurs in ∼25% of individuals with 22q11.2 deletion syndrome (22q11.2DS), the strongest known molecular genetic risk factor for schizophrenia. This review highlights recent literature in 22q11.2DS as it pertains to psychosis and schizophrenia. RECENT FINDINGS: Advances in noninvasive prenatal testing allow for early detection of 22q11.2DS in utero, whereas premature birth has been shown to be a significant risk factor for development of psychotic illness in 22q11...
February 21, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28230276/dissection-of-regulatory-elements-during-direct-conversion-of-somatic-cells-into-neurons
#7
Tahereh Soleimani, Nafiseh Falsafi, Hossein Fallahi
A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230165/mtdna-meta-analysis-reveals-both-phenotype-specificity-and-allele-heterogeneity-a-model-for-differential-association
#8
Shani Marom, Michael Friger, Dan Mishmar
Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230073/%C3%AE-synuclein-transfer-through-tunneling-nanotubes-occurs-in-sh-sy5y-cells-and-primary-brain-pericytes-from-parkinson-s-disease-patients
#9
Birger Victor Dieriks, Thomas I-H Park, Chantelle Fourie, Richard L M Faull, Mike Dragunow, Maurice A Curtis
Parkinson's disease (PD) is characterized by the presence of inclusions known as Lewy bodies, which mainly consist of α-synuclein (α-syn) aggregates. There is growing evidence that α-syn self-propagates in non-neuronal cells, thereby contributing to the progression and spread of PD pathology in the brain. Tunneling nanotubes (TNTs) are long, thin, F-actin-based membranous channels that connect cells and have been proposed to act as conduits for α-syn transfer between cells. SH-SY5Y cells and primary human brain pericytes, derived from postmortem PD brains, frequently form TNTs that allow α-syn transfer and long-distance electrical coupling between cells...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230070/an-fmri-compatible-force-measurement-system-for-the-evaluation-of-the-neural-correlates-of-step-initiation
#10
Andrea Cristina de Lima-Pardini, Raymundo Machado de Azevedo Neto, Daniel Boari Coelho, Catarina Costa Boffino, Sukhwinder S Shergill, Carolina de Oliveira Souza, Rachael Brant, Egberto Reis Barbosa, Ellison Fernando Cardoso, Luis Augusto Teixeira, Rajal G Cohen, Fay Bahling Horak, Edson Amaro
Knowledge of brain correlates of postural control is limited by the technical difficulties in performing controlled experiments with currently available neuroimaging methods. Here we present a system that allows the measurement of anticipatory postural adjustment of human legs to be synchronized with the acquisition of functional magnetic resonance imaging data. The device is composed of Magnetic Resonance Imaging (MRI) compatible force sensors able to measure the level of force applied by both feet. We tested the device in a group of healthy young subjects and a group of elderly subjects with Parkinson's disease using an event-related functional MRI (fMRI) experiment design...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229934/novel-and-functional-atg12-gene-variants-in-sporadic-parkinson-s-disease
#11
Yuequn Li, Jian Huang, Shuchao Pang, Haihua Wang, Aimei Zhang, Robert G Hawley, Bo Yan
Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs)...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229895/impulse-control-disorders-and-levodopa-induced-dyskinesias-in-parkinson-s-disease-an-update
#12
REVIEW
Valerie Voon, T Celeste Napier, Michael J Frank, Veronique Sgambato-Faure, Anthony A Grace, Maria Rodriguez-Oroz, Jose Obeso, Erwan Bezard, Pierre-Olivier Fernagut
Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28229442/-rapidly-progressive-dementia-and-parkinsonism-associated-to-multiple-dural-arteriovenous-fistulas
#13
P Mejia, L M Piedra, X Merchan-Del Hierro
INTRODUCTION: Rapidly progressive dementias are an infrequent group of diseases characterised by cognitive deterioration and other neurological disorders that develop over a period ranging from weeks to months. Their causation is varied and includes a large number of neurodegenerative, toxic, metabolic, autoimmune, infectious and vascular conditions. CASE REPORT: We report the case of a 69-year-old male who was admitted to hospital due to a rapidly progressive dementia and parkinsonism caused by multiple dural arteriovenous fistulas, which were successfully treated by means of endovascular therapy...
March 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28229302/tremor-analysis-separates-parkinson-s-disease-and-dopamine-receptor-blockers-induced-parkinsonism
#14
Aasef G Shaikh
Parkinson's disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson's disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor)...
February 22, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28229223/levodopa-carbidopa-intestinal-gel-lcig-infusion-as-mono-or-combination-therapy
#15
Carsten Buhmann, R Hilker, P Lingor, C Schrader, J Schwarz, M Wolz, H Reichmann
Levodopa/carbidopa intestinal gel (LCIG) infusion is an effective escalating therapy in patients with Parkinson disease (PD) suffering from motor fluctuations and dyskinesia. Levodopa/carbidopa given continuously as infusion provides an optimized application of the most effective and best tolerable antiparkinsonian drug. It has been proven to have a superior motor effect compared with oral levodopa and to improve also non-motor symptoms. However, invasiveness, discomfort resulting from carrying an external device, and side effects associated with the way of administration limit its application in PD patients...
February 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28228718/current-concepts-on-the-physiopathological-relevance-of-dopaminergic-receptors
#16
REVIEW
Ada Ledonne, Nicola B Mercuri
Dopamine (DA) is a key neurotransmitter modulating essential functions of the central nervous system (CNS), like voluntary movement, reward, several cognitive functions and goal-oriented behaviors. The factual relevance of DAergic transmission can be well appreciated by considering that its dysfunction is recognized as a core alteration in several devastating neurological and psychiatric disorders, including Parkinson's disease (PD) and associated movement disorders, as well as, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28228714/narrative-organization-deficit-in-lewy-body-disorders-is-related-to-alzheimer-pathology
#17
Murray Grossman, David J Irwin, Charles Jester, Amy Halpin, Sharon Ash, Katya Rascovsky, Daniel Weintraub, Corey T McMillan
Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28228579/network-wide-oscillations-in-the-parkinsonian-state-alterations-in-neuronal-activities-occur-in-the-premotor-cortex-in-parkinsonian-non-human-primates
#18
Jing Wang, Luke A Johnson, Alicia L Jensen, Kenneth B Baker, Jerrold L Vitek
A number of studies suggest that Parkinson's disease (PD) is associated with alterations of neuronal activity patterns in the basal-ganglia-thalamocortical circuit. There are limited electrophysiological data, however, describing how premotor cortex, which is involved in movement and decision making, is likely impacted in PD. In this study, spontaneous local field potential (LFP) and single unit neuronal activity were recorded in the dorsal premotor area of non-human primates in both the naïve and parkinsonian state using the MPTP model of parkinsonism...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28228566/reduced-cognitive-function-in-patients-with-parkinson-disease-and-obstructive-sleep-apnea
#19
Victoria P Mery, Priti Gros, Anne-Louise Lafontaine, Ann Robinson, Andrea Benedetti, R John Kimoff, Marta Kaminska
OBJECTIVE: To assess the association between obstructive sleep apnea (OSA) and nonmotor symptoms (NMS), including cognitive dysfunction, in patients with Parkinson disease (PD). METHODS: Patients with idiopathic PD, recruited from a movement disorder clinic, underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥15/h. PD severity was assessed using the Hoehn & Yahr (H&Y) scale and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)...
February 22, 2017: Neurology
https://www.readbyqxmd.com/read/28227972/support-vector-machine-classification-of-parkinson-s-disease-and-essential-tremor-subjects-based-on-temporal-fluctuation
#20
Decho Surangsrirat, Chusak Thanawattano, Ronachai Pongthornseri, Songphon Dumnin, Chanawat Anan, Roongroj Bhidayasiri, Decho Surangsrirat, Chusak Thanawattano, Ronachai Pongthornseri, Songphon Dumnin, Chanawat Anan, Roongroj Bhidayasiri, Ronachai Pongthornseri, Roongroj Bhidayasiri, Songphon Dumnin, Chanawat Anan, Chusak Thanawattano, Decho Surangsrirat
Tremor is a common symptom shared in both Parkinson's disease (PD) and Essential tremor (ET) subjects. The differential diagnosis of PD and ET tremor is important since the realization of treatment depends on specific medication. A novel feature is developed based on a hypothesis that tremor of PD subject has a larger fluctuation during resting than action task. Tremor signal is collected using a triaxial gyroscope sensor attached to subject's finger during kinetic and resting task. The angular velocity signal is analyzed by transforming a one-dimensional to two-dimensional signal using a relation of signal and its delay versions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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