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https://www.readbyqxmd.com/read/28527591/the-role-of-astrocyte-dysfunction-in-parkinson-s-disease-pathogenesis
#1
REVIEW
Heather D E Booth, Warren D Hirst, Richard Wade-Martins
Astrocytes are the most populous glial subtype and are critical for brain function. Despite this, historically there have been few studies into the role that they may have in neurodegenerative diseases, such as Parkinson's disease (PD). Recently, however, several studies have determined that genes known to have a causative role in the development of PD are expressed in astrocytes and have important roles in astrocyte function. Here, we review these recent developments and discuss their impact on our understanding of the pathophysiology of PD, and the implications that this might have for its treatment...
May 17, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28521704/dopamine-d2-receptors-dimers-how-can-we-pharmacologically-target-them
#2
Marco Carlia, Shivakumar Kolachalam, Stefano Aringhieri, Mario Rossib, Luca Giovannini, Roberto Maggio, Marco Scarselli
Dopamine D2 and D3 receptors are important pharmacological targets in Schizophrenia and Parkinson's disease. Intriguingly, many studies have shown that they form homo- and heterodimers, and they can be targeted in specific tissues with new drugs. In this direction, many efforts have been made to develop new molecules that are able to interact with these receptor dimeric complexes. Among various strategies for targeting dopamine receptors dimers, two distinct classes of compounds, such as bivalent and bitopic ligands, have gained particular attention and their use in pharmacology looks promising...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28495386/development-of-molecular-tools-based-on-the-dopamine-d3-receptor-ligand-fauc-329-showing-inhibiting-effects-on-drug-and-food-maintained-behavior
#3
Anne Stößel, Regine Brox, Nirupam Purkayastha, Harald Hübner, Carsten Hocke, Olaf Prante, Peter Gmeiner
Dopamine D3 receptor-mediated networks have been associated with a wide range of neuropsychiatric diseases, drug addiction and food maintained behavior, which makes D3 a highly promising biological target. The previously described dopamine D3 receptor ligand FAUC 329 (1) showed protective effects against dopamine depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand [(18)F]2, a [(18)F]fluoroethoxy substituted analog of the lead compound 1 as a molecular tool for visualization of D3-rich brain regions including the islands of Calleja...
April 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28489950/the-return-of-d4-dopamine-receptor-antagonists-in-drug-discovery
#4
Craig W Lindsley, Corey R Hopkins
The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Coupled with genetic association of the DRD4 gene with various CNS disorders, multiple companies launched discovery programs to develop selective D4 antagonists. Merck's D4 antagonist L-745,870 was the first to reach the clinic, where it was found to be ineffective in schizophrenia patients, and other groups failed to recapitulate some of the genetic data...
May 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28480524/stratifying-parkinson-s-patients-with-stn-dbs-into-high-frequency-or-60-hz-frequency-modulation-using-a-computational-model
#5
Anahita Khojandi, Oleg Shylo, Lucia Mannini, Brian H Kopell, Ritesh A Ramdhani
OBJECTIVE: High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for Parkinson's disease (PD), particularly the cardinal motor symptoms and levodopa induced motor complications. Recent studies have suggested the possible role of 60 Hz stimulation in STN-deep brain stimulation (DBS) for patients with gait disorder. The objective of this study was to develop a computational model, which stratifies patients a priori based on symptomatology into different frequency settings (i...
May 8, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28445525/correction-lower-levels-of-uric-acid-and-striatal-dopamine-in-non-tremor-dominant-parkinson-s-disease-subtype
#6
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0174644.].
2017: PloS One
https://www.readbyqxmd.com/read/28441649/home-based-physical-behavior-in-late-stage-parkinson-disease-dementia-differences-between-cognitive-subtypes
#7
Bernhard Cerff, Walter Maetzler, Patricia Sulzer, Malte Kampmeyer, Jos Prinzen, Markus A Hobert, Dominik Blum, Rob van Lummel, Silvia Del Din, Susanne Gräber, Daniela Berg, Inga Liepelt-Scarfone
BACKGROUND: For the early diagnosis of Parkinson disease dementia (PDD), objective home-based tools are needed to quantify even mild stages of dysfunction of the activities of daily living (ADL). OBJECTIVES: In this pilot study, home-based physical behavior was assessed to examine whether it is possible to distinguish mild cognitive impairment (PD-MCI) from PDD. METHODS: Fifty-five patients with mild to severe Parkinson disease (PD) participated in this cross-sectional study...
April 26, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28425642/the-priamo-study-urinary-dysfunction-as-a-marker-of-disease-progression-in-early-parkinson-s-disease
#8
M Picillo, R Palladino, P Barone, R Erro, C Colosimo, R Marconi, L Morgante, A Antonini
BACKGROUND AND PURPOSE: New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life...
April 20, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28420978/resting-state-fmri-reveals-increased-subthalamic-nucleus-and-sensorimotor-cortex-connectivity-in-patients-with-parkinson-s-disease-under-medication
#9
Bo Shen, Yang Gao, Wenbin Zhang, Liyu Lu, Jun Zhu, Yang Pan, Wenya Lan, Chaoyong Xiao, Li Zhang
Functional connectivity (FC) between the subthalamic nucleus (STN) and the sensorimotor cortex is increased in off-medication patients with Parkinson's disease (PD). However, the status of FC between STN and sensorimotor cortex in on-medication PD patients remains unclear. In this study, resting state functional magnetic resonance imaging was employed on 31 patients with PD under medication and 31 healthy controls. Two-sample t-test was used to study the change in FC pattern of the STN, the FC strength of the bilateral STN was correlated with overall motor symptoms, while unilateral STN was correlated with offside motor symptoms...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28416445/%C3%AE-o-conotoxin-gexiva-disulfide-bond-isomers-exhibit-differential-sensitivity-for-various-nicotinic-acetylcholine-receptors-but-retain-potency-and-selectivity-for-the-human-%C3%AE-9%C3%AE-10-subtype
#10
Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Yong Wu, David J Craik, J Michael McIntosh, Sulan Luo
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible isomers...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28409050/correlation-of-mri-visual-scales-with-neuropsychological-profile-in-mild-cognitive-impairment-of-parkinson-s-disease
#11
Luiz Felipe Vasconcellos, João Santos Pereira, Marcelo Adachi, Denise Greca, Manuela Cruz, Ana Lara Malak, Helenice Charchat-Fichman, Mariana Spitz
Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28387684/neuropsychological-subgroups-in-non-demented-parkinson-s-disease-a-latent-class-analysis
#12
Laura Brennan, Kathryn M Devlin, Sharon X Xie, Dawn Mechanic-Hamilton, Baochan Tran, Howard H Hurtig, Alice Chen-Plotkin, Lama M Chahine, James F Morley, John E Duda, David R Roalf, Nabila Dahodwala, Jacqueline Rick, John Q Trojanowski, Paul J Moberg, Daniel Weintraub
BACKGROUND: Methods to detect early cognitive decline and account for heterogeneity of deficits in Parkinson's disease (PD) are needed. Quantitative methods such as latent class analysis (LCA) offer an objective approach to delineate discrete phenotypes of impairment. OBJECTIVE: To identify discrete neurocognitive phenotypes in PD patients without dementia. METHODS: LCA was applied to a battery of 8 neuropsychological measures to identify cognitive subtypes in a cohort of 199 non-demented PD patients...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28384481/cognitive-states-influence-dopamine-driven-aberrant-learning-in-parkinson-s-disease
#13
James F Cavanagh, Andrea A Mueller, Darin R Brown, Jacqueline R Janowich, Jacqueline H Story-Remer, Ashley Wegele, Sarah Pirio Richardson
Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients...
March 20, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28358829/lower-levels-of-uric-acid-and-striatal-dopamine-in-non-tremor-dominant-parkinson-s-disease-subtype
#14
Ismael Huertas, Silvia Jesús, José Antonio Lojo, Francisco Javier García-Gómez, María Teresa Cáceres-Redondo, Juan Manuel Oropesa-Ruiz, Fátima Carrillo, Laura Vargas-Gonzalez, Juan Francisco Martín Rodríguez, Pilar Gómez-Garre, David García-Solís, Pablo Mir
Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels...
2017: PloS One
https://www.readbyqxmd.com/read/28350821/neuropathological-diagnoses-and-clinical-correlates-in-older-adults-in-brazil-a-cross-sectional-study
#15
Claudia K Suemoto, Renata E L Ferretti-Rebustini, Roberta D Rodriguez, Renata E P Leite, Luciana Soterio, Sonia M D Brucki, Raphael R Spera, Tarcila M Cippiciani, Jose M Farfel, Alexandre Chiavegatto Filho, Michel Satya Naslavsky, Mayana Zatz, Carlos A Pasqualucci, Wilson Jacob-Filho, Ricardo Nitrini, Lea T Grinberg
BACKGROUND: Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28324303/subtypes-of-parkinson-s-disease-what-do-they-tell-us-about-disease-progression
#16
REVIEW
Seyed-Mohammad Fereshtehnejad, Ronald B Postuma
Parkinson's disease is a widely heterogeneous disorder with a broad list of motor and nonmotor manifestations. Identifying subtypes of Parkinson's disease is one of the top clinical and research priorities. This review aims to summarize the most valid conventional and recent subtyping solutions that have been introduced so far and to update our current knowledge with recent discoveries on the association between subtypes and disease progression. We also discuss the challenges of subtyping in the context of Parkinson's disease, stability of the subtypes over time, and potential clinical implications...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28324169/roles-of-centromedian-parafascicular-nuclei-of-thalamus-and-cholinergic-interneurons-in-the-dorsal-striatum-in-associative-learning-of-environmental-events
#17
REVIEW
Ko Yamanaka, Yukiko Hori, Takafumi Minamimoto, Hiroshi Yamada, Naoyuki Matsumoto, Kazuki Enomoto, Toshihiko Aosaki, Ann M Graybiel, Minoru Kimura
The thalamus provides a massive input to the striatum, but despite accumulating evidence, the functions of this system remain unclear. It is known, however, that the centromedian (CM) and parafascicular (Pf) nuclei of the thalamus can strongly influence particular striatal neuron subtypes, notably including the cholinergic interneurons of the striatum (CINs), key regulators of striatal function. Here, we highlight the thalamostriatal system through the CM-Pf to striatal CINs. We consider how, by virtue of the direct synaptic connections of the CM and PF, their neural activity contributes to the activity of CINs and striatal projection neurons (SPNs)...
March 21, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28315845/icarus-study-prevalence-and-clinical-features-of-impulse-control-disorders-in-parkinson-s-disease
#18
MULTICENTER STUDY
Angelo Antonini, Paolo Barone, Ubaldo Bonuccelli, Karin Annoni, Mahnaz Asgharnejad, Paolo Stanzione
BACKGROUND: Impulse control disorders/other compulsive behaviours ('ICD behaviours') occur in Parkinson's disease (PD), but prospective studies are scarce, and prevalence and clinical characteristics of patients are insufficiently defined. OBJECTIVES: To assess the presence of ICD behaviours over a 2-year period, and evaluate patients' clinical characteristics. METHODS: A prospective, non-interventional, multicentre study (ICARUS (Impulse Control disorders And the association of neuRopsychiatric symptoms, cognition and qUality of life in ParkinSon disease); SP0990) in treated Italian PD outpatients...
April 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28300069/extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#19
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290191/effects-of-progressive-resistance-exercise-in-akinetic-rigid-parkinson-s-disease-patients-a-randomized-controlled-trial
#20
Luis Santos, Javier Fernandez-Rio, Kristian Winge, Beatriz Barragán-Pérez, Lucía González-Gómez, Vicente Rodríguez-Pérez, Vicente González-Díez, Alejandro Lucía, Eliseo Iglesias-Soler, Xurxo Dopico-Calvo, Miguel Fernández-Del-Olmo, Miguel Del-Valle, Miguel Blanco-Traba, Oscar E Suman, Javier Rodríguez-Gómez
BACKGROUND: Progressive resistance exercise (PRE) can have a positive effect in individuals with Parkinson's disease (PD). However, the effect of PRE may vary with the clinical subtype of PD. To date, no study has assessed the effects of PRE in the different subtypes of PD. AIM: The aim of the present study was to assess the effects of PRE in PD patients with akinesia and rigidity (AR-subtype). DESIGN: A randomized controlled trial was conducted...
March 13, 2017: European Journal of Physical and Rehabilitation Medicine
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