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Chloe Laurencin, Solveig Montaut, Christophe Vial, Lorraine Bernard, Sylvie Bin, Lucie Rascle, Gustavo Polo, Patrick Mertens, Teodor Danaila, Stephane Thobois
BACKGROUND: Off state toe dystonia (TD) is a symptom frequently encountered in Parkinson's disease (PD), but little is known about its evolution after subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVE: To analyze the prevalence and the evolution of TD in PD patients candidate to STN-DBS. METHODS: Individual data of consecutive 130 PD patients who underwent STN-DBS between 2010 and 2015 were collected. RESULTS: Data were successfully collected in 95 patients...
July 12, 2018: Journal of the Neurological Sciences
Malbor Asllani, Paul Expert, Timoteo Carletti
Many collective phenomena in Nature emerge from the -partial- synchronisation of the units comprising a system. In the case of the brain, this self-organised process allows groups of neurons to fire in highly intricate partially synchronised patterns and eventually lead to high level cognitive outputs and control over the human body. However, when the synchronisation patterns are altered and hypersynchronisation occurs, undesirable effects can occur. This is particularly striking and well documented in the case of epileptic seizures and tremors in neurodegenerative diseases such as Parkinson's disease...
July 19, 2018: PLoS Computational Biology
Achut Prasad Silwal, H Peter Lu
Dopamine (DA) is the catecholamine neurotransmitter which interacts with dopamine receptors (DARs) to generate dopaminergic signals in nervous system. Dopamine transporter (DAT) interacts with DA to maintain DA's homeostasis in synaptic and perisynaptic space. DAT and DARs have great importance in central nervous system (CNS) since they are associated to the targeted binding of drugs. Interactions of DA, or its analogue with DARs, or DAT have been studied extensively to understand the mechanism of the dopaminergic signaling process and several neurodegenerative diseases including schizophrenia, Parkinson's diseases, addiction, attention deficit hyperactivity disorder (ADHD), and bipolar disorder...
July 19, 2018: ACS Chemical Neuroscience
Adit Friedberg, Ilana Erikh, Maria Nassar, Elliot Sprecher, Ilana Schlesinger
OBJECTIVE: The aim of this study was to assess clinical response to a high-dose intravenous (IV) amantadine given for 5 consecutive days in patients with multiple system atrophy parkinsonism (MSA-P). METHODS: Subjects with a diagnosis of MSA-P treated with IV amantadine were included. Patients' disease severity before and after therapy was evaluated using the Unified Multiple System Atrophy Rating Scale (UMSARS). RESULTS: Fourteen subjects (8 females) were included...
July 18, 2018: Clinical Neuropharmacology
Merel Verhoeff, Frank Lobbezoo, Peter Wetselaar, Ghizlane Aarab, Michail Koutris
BACKGROUND: Even though bruxism and Parkinson's disease (PD) share common characteristics, their relation is still not clear. Both bruxism and PD are movement disorders in addition, patients with bruxism as well as those with PD complain about musculoskeletal pain, including temporomandibular disorders (TMD) pain. OBJECTIVES: Therefore, the aim of this pilot study was to gain more insight into the possible relation between bruxism and TMD on the one hand and PD on the other...
July 19, 2018: Journal of Oral Rehabilitation
Taira Kajisa, Wei Li, Tsuyoshi Michinobu
A highly sensitive catecholamine (CA) sensor was created using a biointerface layer composed of a biopolymer and a potentiometric detection device. For the detection of CAs, 3-aminophenylboronic acid (3-NH2 -PBA) was reacted with the carboxyl side chain of l-3,4-dihydroxyphenylalanine (l-dopa, LD) and the PBA-modified l-dopa was directly copolymerized with LD on an Au electrode, resulting in a 3.5 nm thick PBA-modified poly(PBA-LD/LD) layer-coated Au electrode. By connecting the PBA-LD-coated Au electrode to a field-effect transistor (FET), the molecular charge changes at the biointerface of the Au electrode, which was caused by di-ester binding of the PBA-CA complex, were transduced into gate surface potential changes...
June 30, 2018: ACS Omega
José A Morales-Garcia, Irene G Salado, Marina Sanz-San Cristobal, Carmen Gil, Ana Pérez-Castillo, Ana Martínez, Daniel I Pérez
Parkinson's disease (PD), an age-related neurodegenerative disorder that results from a progressive loss of dopaminergic neurons has an enormous economical and human cost. Unfortunately, only symptomatic treatment such as dopamine replacement therapy is available. Therefore, drugs with new mechanisms of action able to protect against neuronal cell death are an urgent need. We here report the in vivo efficacy on dopaminergic neuronal protection in a PD mouse model and the lack of toxicity in zebrafish and Ames test of benzothiazole-based casein kinase-1δ (CK-1δ) nanomolar inhibitors...
August 31, 2017: ACS Omega
Daniel Nir Bloch, Yifat Miller
Parkinson's disease is characterized by the self-assembly of α-synuclein (AS), in which its aggregates accumulate in the substantia nigra. The molecular mechanisms of the self-assembly of AS are challenging because AS is a relatively large intrinsically disordered protein, consisting of 140 residues. It is known that the N-termini of AS contribute to the toxicity of the proteins; therefore, it is important to investigate the self-assembly structure of the N-termini on AS as well. There have been extensive efforts to investigate the structural fibrils of AS(1-140), which have shown that the N-termini are disordered and do not participate in the fibrillary structure...
July 31, 2017: ACS Omega
Patrick L Donabedian, Mallory Evanoff, Florencia A Monge, David G Whitten, Eva Y Chi
Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer's and Parkinson's diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure-function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin...
July 31, 2017: ACS Omega
Ana Vives-Rodriguez, Elan D Louis
Objective: To investigate the prevalence of index finger pointing (IFP) while walking, which is likely a subtle form of hand dystonia, in cranio-cervical focal dystonia syndromes, Parkinson's disease (PD), essential tremor (ET), and controls. Methods: We recruited patients with an established diagnosis of PD, dystonia, or ET and healthy controls. All participants were videotaped while walking. Videotapes were evaluated by the authors, blinded to diagnosis, to assess the presence or absence of IFP. Results: Two-hundred-fifty participants included 50 dystonia, 50 PD, 80 ET and 70 controls...
2018: Frontiers in Neurology
Dong Hwan Ho, A Reum Je, Haejin Lee, Ilhong Son, Hee-Seok Kweon, Hyung-Gun Kim, Wongi Seol
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia...
June 2018: Experimental Neurobiology
Keila Bariotto-Dos-Santos, Fernando Eduardo Padovan-Neto, Mariza Bortolanza, Maurício Dos-Santos-Pereira, Rita Raisman-Vozari, Vitor Tumas, Elaine Del Bel
The nitric oxide (NO) system has been proven to be a valuable modulator of L-DOPA-induced dyskinesia in parkinsonian rodents. NO activates the enzyme soluble guanylyl cyclase and elicits the synthesis of the second messenger cGMP. Although we have previously described the anti-dyskinetic potential of NO synthase inhibitors on L-DOPA-induced dyskinesia, the effect of soluble guanylyl cyclase inhibitors remains to be evaluated. The aim of the present study was to analyze whether the clinically available non-selective inhibitor methylene blue, or the selective soluble guanylyl cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), could mitigate L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats...
July 18, 2018: European Journal of Neuroscience
Michael J Firbank, Jehill Parikh, Nicholas Murphy, Alison Killen, Charlotte L Allan, Daniel Collerton, Andrew M Blamire, John-Paul Taylor
OBJECTIVE: To investigate the relationship between visual hallucinations in Parkinson disease (PD) and levels of γ-aminobutyric acid (GABA) in the primary visual cortex. METHODS: We utilized magnetic resonance spectroscopy to investigate occipital GABA levels in 36 participants with PD, 19 with and 17 without complex visual hallucinations, together with 20 healthy controls without hallucinations. In addition, we acquired T1-weighted MRI, whole-brain fMRI during a visual task, and diffusion tensor imaging...
July 18, 2018: Neurology
Marco Onofrj, Gordon J Gilbert
No abstract text is available yet for this article.
July 18, 2018: Neurology
Petra Weimers, Jonas Halfvarson, Michael C Sachs, Jonas F Ludvigsson, Inga Peter, Ola Olén, Johan Burisch
No abstract text is available yet for this article.
July 18, 2018: Gut
Yuriko Kojima, Tomohiro Kumagai, Tomoo Hidaka, Takeyasu Kakamu, Shota Endo, Yayoi Mori, Tadashi Tsukamoto, Takashi Sakamoto, Miho Murata, Takehito Hayakawa, Tetsuhito Fukushima
BACKGROUND: The facial expression of medical staff has been known to greatly affect the psychological state of patients, making them feel uneasy or conversely, cheering them up. By clarifying the characteristics of facial expression recognition ability in patients with Lewy body disease, the aim of this study is to examine points to facilitate smooth communication between caregivers and patients with the disease whose cognitive function has deteriorated. METHODS: During the period from March 2016 to July 2017, we examined the characteristics of recognition of the six facial expressions of "happiness," "sadness," "fear," "anger," "surprise," and "disgust" for 107 people aged 60 years or more, both outpatient and inpatient, who hospital specialists had diagnosed with Lewy body diseases of Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies...
July 18, 2018: Environmental Health and Preventive Medicine
Paul Lingor, Joseph Claßen, Heinz Herbst, Alexander Storch, Peter Urban, Ingmar Wellach, Wolfgang H Jost
Patients with Parkinson's disease show a wide heterogeneity of symptoms and comorbidities, requiring individualized therapeutic strategies, particularly in advanced stages of the disease. This is reflected by the choice of different substance classes and drugs for the treatment of end-of-dose fluctuations. Each of these drugs offers a characteristic profile of effects and unwanted side-effects, which has to be taken into consideration. Replacement of a substance by an alternative drug under consideration, for instance, of healthcare economics is possible only to a limited extent, since therapeutic effects as well as tolerability in the individual patient must be taken into account...
July 18, 2018: Fortschritte der Neurologie-Psychiatrie
Issa Olakunle Yusuf, Pei-Hsun Cheng, Hsiu-Mei Chen, Yu-Fan Chang, Chih-Yi Chang, Han-In Yang, Chia-Wei Lin, Shaw-Jenq Tsai, Jih-Ing Chuang, Chia-Ching Wu, Bu-Miin Huang, H Sunny Sun, Shang-Hsun Yang
BACKGROUND/AIMS: Huntington's disease (HD) is a heritable neurodegenerative disorder, and there is no cure for HD to date. A type of fibroblast growth factor (FGF), FGF9, has been reported to play prosurvival roles in other neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. However, the effects of FGF9 on HD is still unknown. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD...
July 18, 2018: Cellular Physiology and Biochemistry
Thomas Mund, Masami Masuda-Suzukake, Michel Goedert, Hugh R Pelham
Alpha-synuclein can form beta-sheet filaments, the accumulation of which plays a key role in the development of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. It has previously been shown that alpha-synuclein is a substrate for the HECT domain-containing ubiquitin ligase Nedd4, and is subject to ubiquitin-mediated endosomal degradation. We show here that alpha-synuclein filaments are much better substrates for ubiquitination in vitro than monomeric alpha-synuclein, and that this increased susceptibility cannot be mimicked by the mere clustering of monomers...
2018: PloS One
Nicholas Maling, Scott F Lempka, Zack Blumenfeld, H M Bronte-Stewart, Cameron C McIntyre
Clinical deep brain stimulation (DBS) technology is evolving to enable chronic recording of local field potentials (LFPs) that represent electrophysiological biomarkers of the underlying disease state. However, little is known about the biophysical basis of LFPs, or how the patient's unique brain anatomy and electrode placement impact the recordings. Therefore, we developed a patient-specific computational framework to analyze LFP recordings within a clinical DBS context. We selected a subject with Parkinson's disease implanted with a Medtronic Activa PC+S DBS system and reconstructed their subthalamic nucleus (STN) and DBS electrode location using medical imaging data...
July 18, 2018: Journal of Neurophysiology
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