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Parkinson's Foundation

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https://www.readbyqxmd.com/read/29305429/back-to-the-future-new-target-validated-rab-antibodies-for-evaluating-lrrk2-signalling-in-cell-biology-and-parkinson-s-disease
#1
Patrick A Eyers
The addition of phosphate groups to substrates allows protein kinases to regulate a myriad of biological processes, and contextual analysis of protein-bound phosphate is important for understanding how kinases contribute to physiology and disease. Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase linked to familial and sporadic cases of Parkinson's disease (PD). Recent work established that multiple Rab GTPases are physiological substrates of LRRK2, with Rab10 in particular emerging as a human substrate whose site-specific phosphorylation mirrors hyperactive LRRK2 lesions associated with PD...
January 5, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29230295/modulating-protein-amyloid-aggregation-with-nanomaterials
#2
Bo Wang, Emily H Pilkington, Yunxiang Sun, Thomas P Davis, Pu Chun Ke, Feng Ding
Direct exposure or intake of nanopaticles (NPs) to the human body can invoke a series of biological responses, some of which are deleterious, and as such the role of NPs in vivo requires thorough examination. Over the past decade, it has been established that biomolecules such as proteins can bind NPs to form a 'corona', where the structures and dynamics of NP-associated proteins can assign new functionality, systemic distribution and toxicity. However, the behavior and fate of NPs in biological systems are still far from being fully understood...
September 1, 2017: Environmental Science. Nano
https://www.readbyqxmd.com/read/29228074/a-review-of-the-current-therapies-challenges-and-future-directions-of-transcranial-focused-ultrasound-technology-advances-in-diagnosis-and-treatment
#3
Vibhor Krishna, Francesco Sammartino, Ali Rezai
Importance: Magnetic resonance imaging-guided focused ultrasound ablation has been approved for the treatment of refractory essential tremor and is being studied for other neurological indications, including dyskinesias and tremor in Parkinson disease, dystonia, neuropathic pain, obsessive-compulsive disorder, epilepsy, and brain tumors. Objective: To review the scientific foundations of FUS technology, existing neurological applications, and future advances. Evidence Review: PubMed was searched for the past 10 years using the terms "transcranial ultrasound," "focused ultrasound," and "neurological applications...
December 11, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29196580/sex-disparities-in-access-to-caregiving-in-parkinson-disease
#4
Nabila Dahodwala, Krunal Shah, Ying He, Samuel S Wu, Peter Schmidt, Fernando Cubillos, Allison W Willis
OBJECTIVE: To compare access to caregiving between men and women with Parkinson disease (PD). METHODS: This was a cross-sectional and longitudinal study among participants with PD enrolled in the National Parkinson Foundation Parkinson's Outcomes Project from 2009 to 2014 at 21 international sites. The primary outcome measures were presence of a caregiver at the baseline visit, caregiver burden as measured by the Multidimensional Caregiver Strain Index (MCSI) at baseline, and time to first paid caregiver...
December 1, 2017: Neurology
https://www.readbyqxmd.com/read/29191831/structural-features-of-%C3%AE-synuclein-amyloid-fibrils-revealed-by-raman-spectroscopy
#5
Jessica D Flynn, Ryan P McGlinchey, Robert L Walker, Jennifer C Lee
Parkinson's disease (PD) is associated with the formation of α-synuclein amyloid fibrils. Elucidating the role of these β-sheet-rich fibrils in disease progression is crucial; however, collecting detailed structural information on amyloids is inherently difficult due to their insoluble, non-crystalline, and polymorphic nature. Here, we show that Raman spectroscopy is a facile technique for characterizing structural features of α-synuclein fibrils. Combining Raman spectroscopy with aggregation kinetics and transmission electron microscopy (TEM), we examined the effects of pH and ionic strength as well as four PD-related mutations (A30P, E46K, G51D, and A53T) on α-synuclein fibrils...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29159192/sex-differences-in-lrrk2-g2019s-and-idiopathic-parkinson-s-disease
#6
Marta San Luciano, Cuiling Wang, Roberto A Ortega, Nir Giladi, Karen Marder, Susan Bressman, Rachel Saunders-Pullman
Objective: To evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD). Methods: 530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women...
November 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29144156/upmc-prescription-for-wellness-a-quality-improvement-case-study-for-supporting-patient-engagement-and-health-behavior-change
#7
Rebecca J Maners, Eric Bakow, Michael D Parkinson, Gary S Fischer, Geoffrey R Camp
Addressing patient health and care behaviors that underlie much of chronic disease continues to challenge providers, medical practices, health systems, and insurers. Improving health and care as described by the Quadruple Aim requires innovation at the front lines of clinical care: the doctor-patient interaction and office practice. This article describes the use of Lean Six Sigma in a quality improvement (QI) effort to design an effective and scalable method for physicians to prescribe health coaching for healthy behaviors in a primary care medical home within a large integrated delivery and financing system...
November 1, 2017: American Journal of Medical Quality: the Official Journal of the American College of Medical Quality
https://www.readbyqxmd.com/read/29114657/chemistry-of-mammalian-metallothioneins-and-their-interaction-with-amyloidogenic-peptides-and-proteins
#8
Elena Atrián-Blasco, Alice Santoro, Dean L Pountney, Gabriele Meloni, Christelle Hureau, Peter Faller
Cu and Zn ions are essential in most living beings. Their metabolism is critical for health and mis-metabolism can be lethal. In the last two decades, a large body of evidence has reported the role of copper, zinc and iron, and oxidative stress in several neurodegenerative diseases like Alzheimer's, Parkinson's, prion diseases, etc. To what extent this mis-metabolism is causative or a consequence of these diseases is still a matter of research. In this context metallothioneins (MTs) appear to play a central gate-keeper role in controlling aberrant metal-protein interactions...
November 8, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/29109055/characterization-of-oromotor-and-limb-motor-dysfunction-in-the-dj1-model-of-parkinson-disease
#9
Katie M Yang, Katherine V Blue, Haleigh M Mulholland, Meghna P Kurup, Cynthia A Kelm-Nelson, Michelle R Ciucci
Parkinson disease (PD) is devastating to sensorimotor function that includes cranial/oromotor and limb motor deficits. However, the onset, progression, and neural correlates of PD-related dysfunctions are poorly understood. To address this gap, we used a genetic rat model of PD, DJ1 -/-, and hypothesized that motor deficits would manifest early in the disease process, be progressive in nature, and be related to pathologies in brainstem structures associated with sensorimotor function. The present study compares homozygous DJ1 -/- male rats to age-matched wild type controls...
November 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29103052/increasing-efficiency-of-recruitment-in-early-parkinson-s-disease-trials-a-case-study-examination-of-the-steady-pd-iii-trial
#10
Sarah Berk, Brittany L Greco, Kevin Biglan, Catherine M Kopil, Robert G Holloway, Claire Meunier, Tanya Simuni
BACKGROUND: Challenges in clinical trial recruitment threaten the successful development of improved therapies. This is particularly true in Parkinson's disease (PD) studies of disease modification where the population of interest is difficult to find and study design is more complex. OBJECTIVE: This paper seeks to understand how STEADY PD III, a National Institute of Neurological Disorders and Stroke (NINDS) funded phase 3 trial evaluating the efficacy of isradipine as a disease modifying agent for PD, was able to recruit their full target population 6 months ahead of schedule...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28958801/large-scale-identification-of-clinical-and-genetic-predictors-of-motor-progression-in-patients-with-newly-diagnosed-parkinson-s-disease-a-longitudinal-cohort-study-and-validation
#11
Jeanne C Latourelle, Michael T Beste, Tiffany C Hadzi, Robert E Miller, Jacob N Oppenheim, Matthew P Valko, Diane M Wuest, Bruce W Church, Iya G Khalil, Boris Hayete, Charles S Venuto
BACKGROUND: Better understanding and prediction of progression of Parkinson's disease could improve disease management and clinical trial design. We aimed to use longitudinal clinical, molecular, and genetic data to develop predictive models, compare potential biomarkers, and identify novel predictors for motor progression in Parkinson's disease. We also sought to assess the use of these models in the design of treatment trials in Parkinson's disease. METHODS: A Bayesian multivariate predictive inference platform was applied to data from the Parkinson's Progression Markers Initiative (PPMI) study (NCT01141023)...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28931491/global-regional-and-national-burden-of-neurological-disorders-during-1990-2015-a-systematic-analysis-for-the-global-burden-of-disease-study-2015
#12
(no author information available yet)
BACKGROUND: Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28930542/deep-brain-stimulation-foundations-and-future-trends
#13
David J Aum, Travis S Tierney
Deep brain stimulation (DBS) has emerged as a revolutionary treatment option for essential tremor (ET), Parkinson's disease (PD), idiopathic dystonia, and severe obsessive-compulsive disorder (OCD). This article reviews the historical foundations of DBS including basal ganglia pathophysiological models, classic principles of electrical stimulation, technical components of the DBS system, treatment risks, and future directions for DBS. Chronic high frequency stimulation induces a number of functional changes from fast physiological to slower metabolic effects and ultimately leads to structural reorganization of the brain, so-called neuroplasticity...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28829278/glucose-6-phosphatase-%C3%AE-participates-in-dopaminergic-differentiation
#14
Jing Chen, Ting Wang, Xiao-Yan Zhou, Chuan-Xi Tang, Dian-Shuai Gao
OBJECTIVE:  Induction of dopaminergic (DA) differentiation is a cell-based therapy for Parkinson's disease (PD). Here, we explore the key factors of DA differentiation with a focus on glucose-6-phosphatase (G6Pase), a marker enzyme for the endoplasmic reticulum (ER) associated with cell differentiation. METHODS:  We cultured SH-SY5Y human neuroblastoma cells, a model system for PD research, and added glial cell-derived neurotrophic factor (GDNF; 25, 50, or 100 ng/ml) to stimulate differentiation...
August 22, 2017: Neurological Research
https://www.readbyqxmd.com/read/28800338/a-guideline-for-parkinson-s-disease-nurse-specialists-with-recommendations-for-clinical-practice
#15
Herma Lennaerts, Marieke Groot, Berna Rood, Koen Gilissen, Hella Tulp, Erik van Wensen, Marten Munneke, Teus van Laar, Bastiaan R Bloem
BACKGROUND: Parkinson's Disease Nurse Specialists (PDNS) play an important role in the care for patients with Parkinson's disease (PD) and their caregivers. Until now, there were no nursing guidelines in PD, and interventions were based solely on daily clinical practice because there is no evidence to support the merits of nursing interventions. Consequently, there is little uniformity in current care delivery. OBJECTIVE: Developing a guideline for PDNS. METHODS: We developed a guideline based on a questionnaire among PDNS and a literature review, supplemented with expert opinion plus the input of patients and caregivers...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28781108/exenatide-once-weekly-versus-placebo-in-parkinson-s-disease-a-randomised-double-blind-placebo-controlled-trial
#16
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
October 7, 2017: Lancet
https://www.readbyqxmd.com/read/28772097/what-have-we-learned-about-movement-disorders-from-functional-neurosurgery
#17
Andres M Lozano, William D Hutchison, Suneil K Kalia
Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders...
July 25, 2017: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/28743576/a-review-on-protein-misfolding-aggregation-and-strategies-to-prevent-related-ailments
#18
REVIEW
Tooba Naz Shamsi, Teeba Athar, Romana Parveen, Sadaf Fatima
This review aims to highlight the fundamental mechanism of protein misfolding leading to protein aggregation and associated diseases. It also aims to anticipate novel therapeutic strategies with which to prevent or treat these highly debilitating conditions linked to these pathologies. The failure of a protein to correctly fold de novo or to remain correctly folded can have profound consequences on a living system especially when the cellular quality control processes fail to eliminate the rogue proteins. The core cause of over 20 different human diseases which have now been designated as 'conformational diseases' including neurodegenerative diseases such as Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD) etc...
December 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28735833/cannabis-use-in-people-with-parkinson-s-disease-and-multiple-sclerosis-a-web-based-investigation
#19
John H Kindred, Kaigang Li, Nathaniel B Ketelhut, Felix Proessl, Brett W Fling, Justin M Honce, William R Shaffer, Thorsten Rudroff
OBJECTIVES: Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. METHODS: An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016...
August 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/28734051/a-user-s-guide-for-%C3%AE-synuclein-biomarker-studies-in-biological-fluids-perianalytical-considerations
#20
REVIEW
Brit Mollenhauer, Richard Batrla, Omar El-Agnaf, Douglas R Galasko, Hilal A Lashuel, Kalpana M Merchant, Lesley M Shaw, Dennis J Selkoe, Robert Umek, Hugo Vanderstichele, Henrik Zetterberg, Jing Zhang, Chelsea Caspell-Garcia, Chris Coffey, Samantha J Hutten, Mark Frasier, Peggy Taylor
Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α-synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods...
August 2017: Movement Disorders: Official Journal of the Movement Disorder Society
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