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Parkinson‘s disease

Akiko Sumitomo, Kouta Horike, Kazuko Hirai, Nancy Butcher, Erik Boot, Takeshi Sakurai, Frederick C Nucifora, Anne S Bassett, Akira Sawa, Toshifumi Tomoda
Individuals with chromosome 22q11.2 deletions are at increased risk of developing psychiatric conditions, most notably, schizophrenia (SZ). Recently, clinical studies have also implicated these recurrent 22q11.2 deletions with the risk of early-onset Parkinson's disease (PD). Thus far, the multiple mouse models generated for 22q11.2 deletions have been studied primarily in the context of congenital cardiac, neurodevelopmental, and psychotic disorders. One of these is the Df1 /+ model, in which SZ-associated and developmental abnormalities have been reported...
August 2018: Science Advances
Katriana A Popichak, Sean L Hammond, Julie A Moreno, Maryam F Afzali, Donald S Backos, Richard D Slayden, Steven Safe, Ronald B Tjalkens
Inflammatory activation of glial cells promotes loss of dopaminergic neurons in Parkinson's disease (PD). The transcription factor, Nuclear Factor-kappa B (NF-κB), regulates the expression of multiple neuroinflammatory cytokines and chemokines in activated glial cells that are damaging to neurons. Thus, inhibition of NF-κB signaling in glial cells could be a promising therapeutic strategy for the prevention of neuroinflammatory injury. Nuclear orphan receptors in the NR4A family, including NR4A1 (Nur77) and NR4A2 (Nurr1), can inhibit the inflammatory effects of NFκB but there are no approved drugs that target these receptors...
August 15, 2018: Molecular Pharmacology
Alice S Chen-Plotkin, Roger Albin, Roy Alcalay, Debra Babcock, Vikram Bajaj, Dubois Bowman, Alex Buko, Jesse Cedarbaum, Daniel Chelsky, Mark R Cookson, Ted M Dawson, Richard Dewey, Tatiana Foroud, Mark Frasier, Dwight German, Katrina Gwinn, Xuemei Huang, Catherine Kopil, Thomas Kremer, Shirley Lasch, Ken Marek, Jarrod A Marto, Kalpana Merchant, Brit Mollenhauer, Anna Naito, Judith Potashkin, Alyssa Reimer, Liana S Rosenthal, Rachel Saunders-Pullman, Clemens R Scherzer, Todd Sherer, Andrew Singleton, Margaret Sutherland, Ines Thiele, Marcel van der Brug, Kendall Van Keuren-Jensen, David Vaillancourt, David Walt, Andrew West, Jing Zhang
The recent advent of an "ecosystem" of shared biofluid sample biorepositories and data sets will focus biomarker efforts in Parkinson's disease, boosting the therapeutic development pipeline and enabling translation with real-world impact.
August 15, 2018: Science Translational Medicine
Olga Klepitskaya, Ying Liu, Saloni Sharma, Stefan H Sillau, Jean Tsai, Arthur S Walters
OBJECTIVE: To study the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease (PD) and moderate to severe restless legs syndrome (RLS) on their RLS symptoms. METHODS: Patients undergoing STN DBS surgery for PD completed the International RLS Study Group Rating Scale (IRLS) and RLS Quality of Life (QoL) questionnaires preoperatively and postoperatively at 6 months, 1 year, and 2 years. The primary outcome measure was IRLS sum score and subscales (severity and impact) and the secondary measure was RLS QoL scores...
August 15, 2018: Neurology
Luiz M Oliveira, Barbara Falquetto, Thiago S Moreira, Ana C Takakura
Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra compacta (SNpc) and the only risk factor is aging. We showed that in 6-hydroxydopamine (6-OHDA)-model of PD there is a reduction in the neuronal profile within the brainstem ventral respiratory column with a decrease in the hypercapnic ventilatory response. Here we tested the involvement of orexin cells from the lateral hypothalamus/perifornical area (LH/PeF) on breathing in a 6-OHDA PD model...
August 12, 2018: Experimental Neurology
Amritha Gourisankar, Sarah A Eisenstein, Nicholas T Trapp, Jonathan M Koller, Meghan C Campbell, Mwiza Ushe, Joel S Perlmutter, Tamara Hershey, Kevin J Black
The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patient's clinically optimized DBS settings and active contact...
July 2018: Royal Society Open Science
Sachchida N Rai, Saumitra S Singh, Hareram Birla, Walia Zahra, Aaina S Rathore, Payal Singh, Surya P Singh
No abstract text is available yet for this article.
2018: Frontiers in Aging Neuroscience
Thomas G Beach, Geidy E Serrano, Thomas Kremer, Marta Canamero, Sebastian Dziadek, Hadassah Sade, Pascal Derkinderen, Anne-Gaëlle Corbillé, Franck Letournel, David G Munoz, Charles L White, Julie Schneider, John F Crary, Lucia I Sue, Charles H Adler, Michael J Glass, Anthony J Intorcia, Jessica E Walker, Tatiana Foroud, Christopher S Coffey, Dixie Ecklund, Holly Riss, Jennifer Goßmann, Fatima König, Catherine M Kopil, Vanessa Arnedo, Lindsey Riley, Carly Linder, Kuldip D Dave, Danna Jennings, John Seibyl, Brit Mollenhauer, Lana Chahine
Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues...
August 13, 2018: Journal of Neuropathology and Experimental Neurology
Haidar S Dafsari, K Ray Chaudhuri, Picabo Mahlstedt, Lena Sachse, Julia K Steffen, Jan Niklas Petry-Schmelzer, Till A Dembek, Paul Reker, Michael T Barbe, Veerle Visser-Vandewalle, Gereon R Fink, Lars Timmermann
BACKGROUND: In advanced Parkinson's disease (PD), subthalamic neurostimulation (STN-DBS) improves quality of life (QoL), motor, and non-motor symptoms. However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and quality of life in PD is unclear. METHODS: In this prospective, observational study of 39 PD patients undergoing STN-DBS, we examined PDQuestionnaire-8 (PDQ-8), Toronto Alexithymia Scale-20 (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified PD Rating Scale-activities of daily living, -motor examination, and -complications (UPDRS-II/-III/-IV), and levodopa-equivalent daily dose (LEDD) preoperatively and at 5-month follow-up...
August 14, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Ebtisam A Al-Ofi, Badrah S Al-Ghamdi
Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. In addition to its pathogenic ligands, toll-like receptors (TLRs) can be activated by damaged endogenous molecules that induce inflammatory signalling pathways such as high-mobility group box 1 protein (HMGB1). Using an ex-vivo rat optic nerve (RON) model, we sought to determine the effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or HMGB1-with or without TLR2/4 antagonists, on the expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-ҡβ) for signalling pathway and astrocyte reactivity, using double immunohistochemistry; as well as on the modulation of the neurotoxicity...
August 14, 2018: Folia Morphologica (Warsz)
Paulo Pinares-Garcia, Marielle Stratikopoulos, Alice Zagato, Hannah Loke, Joohyung Lee
Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely considered when making treatment decisions in neurological disorders. A better understanding of the molecular mechanism(s) underlying sex differences in the healthy and diseased brain will help to devise diagnostic and therapeutic strategies optimal for each sex...
August 13, 2018: Brain Sciences
Chao Liu, Cheng-Wu Zhang, Shun Qiang Lo, Seok Ting Ang, Katherine Chee Meng Chew, Dejie Yu, Bing Han Chai, Bobby Tan, Fai Tsang, Yee Kit Tai, Bryce Wei Quan Tan, Mui Cheng Liang, Hwee Tong Tan, Jia Ying Tang, Mitchell Kim Peng Lai, John Jia En Chua, Maxey Ching Ming Chung, Sanjay Khanna, Kah-Leong Lim, Tuck Wah Soong
Elevated iron deposition has been reported in Parkinson's disease. However, the route of iron uptake leading to high deposition in the substantia nigra is unresolved. Here, we show a mechanism in enhanced Fe2+ uptake via S-nitrosylation of DMT1. While DMT1 could be S-nitrosylated by exogenous nitric oxide donors, in human PD brains, endogenously S-nitrosylated DMT1 was detected in post-mortem substantia nigra. Patch-clamp electrophysiological recordings and iron uptake assays confirmed increased Mn2+ or Fe2+ uptake through S-nitrosylated DMT1...
August 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
P Perez-Pardo, H B Dodiya, P A Engen, A Naqib, C B Forsyth, S J Green, J Garssen, A Keshavarzian, A D Kraneveld
The mechanism of neurodegeneration in Parkinson's disease (PD) remains unknown but it has been hypothesised that the intestinal tract could be an initiating and contributing factor to the neurodegenerative processes. In PD patients as well as in animal models for PD, alpha-synuclein-positive enteric neurons in the colon and evidence of colonic inflammation have been demonstrated. Moreover, several studies reported pro-inflammatory bacterial dysbiosis in PD patients. Here, we report for the first time significant changes in the composition of caecum mucosal associated and luminal microbiota and the associated metabolic pathways in a rotenone-induced mouse model for PD...
August 13, 2018: Beneficial Microbes
Thomaz F S Bastiaanssen, Caitlin S M Cowan, Marcus J Claesson, Timothy G Dinan, John F Cryan
Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract thus it is not surprising that most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body...
August 7, 2018: International Journal of Neuropsychopharmacology
Deborah Jehu, Julie Nantel
BACKGROUND: The relationship between falls and static and dynamic postural control has not been established in Parkinson's disease (PD). The purpose was to compare the compensatory postural strategies among fallers and non-fallers with PD as well as older adults during static and dynamic movements. METHODS: Twenty-five individuals with PD (11 fallers) and 17 older adults were outfitted with 6 accelerometers on the wrists, ankles, lumbar spine, and sternum, stood quietly for 30 s on a force platform, and walked back and forth for 30 s along a 15 m walkway...
August 3, 2018: Gait & Posture
O V Nevzglyadova, E V Mikhailova, A V Artemov, Y E Ozerova, P A Ivanova, I M Golomidov, O I Bolshakova, V V Zenin, E I Kostyleva, T R Soidla, S V Sarantseva
Recently, we identified the yeast red pigment (RP), a polymer of 1-(5'-Phosphoribosyl)-5-aminoimidazole, as a novel potential anti-amyloid agent for the therapy of neurodegenerative diseases. The purpose of this study was to further validate RP for treatment of Parkinson's disease (PD) and to clarify molecular mechanisms involved in the reduction of amyloid cytotoxicity. We investigated RP effects in vivo using Saccharomyces cerevisiae and Drosophila melanogaster PD models. Western blot analysis revealed reduction in the levels of insoluble α-synuclein in both models, while soluble α-synuclein decreased only in Drosophila...
August 9, 2018: Neurochemistry International
Giulia Boscutti, Eugenii A Rabiner, Christophe Plisson
The development of β+ emitter tracers labelled with carbon-11 or fluorine-18 having optimal characteristics of affinity and selectivity for the phosphodiesterase 10 A protein has received considerable attention, due to the major implication of this enzyme in neurological and psychiatric disorders, such as Hungtington's disease, Parkinson's disease and schizophrenia. The ability to quantify PDE10 A availability in the human brain in vivo will thus aid understanding its role in neurodegenerative and neuropsychiatric pathophysiology as well as providing a valuable tool for drug development...
August 9, 2018: Neuroscience Letters
Matthew C L Phillips, Deborah K J Murtagh, Linda J Gilbertson, Fredrik J S Asztely, Christopher D P Lynch
BACKGROUND: Preliminary evidence suggests that diet manipulation may influence motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to carbohydrate ratio. OBJECTIVES: We designed a pilot randomized, controlled trial to compare the plausibility, safety, and efficacy of a low-fat, high-carbohydrate diet versus a ketogenic diet in a hospital clinic of PD patients. METHODS: We developed a protocol to support PD patients in a diet study and randomly assigned patients to a low-fat or ketogenic diet...
August 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Susan R Criswell, Mark N Warden, Susan Searles Nielsen, Joel S Perlmutter, Stephen M Moerlein, Lianne Sheppard, Jason Lenox-Krug, Harvey Checkoway, Brad A Racette
OBJECTIVE: To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [11 C](N-methyl)benperidol (NMB) PET. METHODS: We used NMB PET to evaluate 50 workers with a range of Mn exposure: 22 Mn-exposed welders, 15 Mn-exposed workers, and 13 nonexposed workers. Cumulative Mn exposure was estimated from work histories, and movement disorder specialists examined all workers. We calculated NMB D2R nondisplaceable binding potential (BPND) for the striatum, globus pallidus, thalamus, and substantia nigra (SN)...
August 10, 2018: Neurology
Valerie Lee, Judy S Wang, Marianna L Zahurak, Elske C Gootjes, Henk M W Verheul, Rose M Parkinson, Zachary Kerner, Anup Sharma, Gary L Rosner, Ana De Jesus-Acosta, Daniel A Laheru, Dung T Le, Aram Oganesian, Ellen Lilly-Foreman, Thomas Brown, Peter A Jones, Stephen B Baylin, Nita Ahuja, Nilofer A Azad
PURPOSE: Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of resistance with administration of hypomethylating agents. We evaluated the safety and tolerability of guadecitabine and irinotecan in mCRC patients previously treated with irinotecan. EXPERIMENTAL DESIGN: In this 3+3 dose-escalation study, mCRC patients previously exposed to irinotecan received guadecitabine days 1-5 of a 28 day cycle and irinotecan 125mg/m2 days 8 and 15 [dose level (DL) 1, guadecitabine 45mg/m2; DL -1: guadecitabine 30mg/m2; DL -1G: guadecitabine 30mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45mg/m2 with GFS...
August 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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