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Parkinson's Foundation

Pei-Lin Lee, Kun-Hsien Chou, Cheng-Hsien Lu, Hsiu-Ling Chen, Nai-Wen Tsai, Ai-Ling Hsu, Meng-Hsiang Chen, Wei-Che Lin, Ching-Po Lin
OBJECTIVES: To identify disease-related spatial covariance patterns of grey matter volume as an aid in the classification of Parkinson's disease (PD). METHODS: Seventy structural covariance networks (SCNs) based on grey matter volume covariance patterns were defined using independent component analysis with T1-weighted structural MRI scans (discovery sample, 70 PD patients and 70 healthy controls). An image-based classifier was constructed from SCNs using a multiple logistic regression analysis with a leave-one-out cross-validation-based feature selection scheme...
March 12, 2018: European Radiology
Yiwei Qian, Xiaodong Yang, Shaoqing Xu, Chunyan Wu, Yanyan Song, Nan Qin, Sheng-Di Chen, Qin Xiao
Emerging evidences suggest that gut microbiota dysbiosis plays a role in Parkinson's disease (PD). However, the alterations in fecal microbiome in Chinese PD patients remains unknown. This case-control study was conducted to explore fecal microbiota compositions in Chinese PD patients. Microbiota communities in the feces of 45 patients and their healthy spouses were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between fecal microbiota and PD clinical characteristics were analyzed...
March 1, 2018: Brain, Behavior, and Immunity
Aimee E Morris, Scott A Norris, Joel S Perlmutter, Jonathan W Mink
BACKGROUND: Focal embouchure dystonia impairs orofacial motor control in wind musicians and causes professional disability. A paucity of quantitative measures or rating scales impedes the objective assessment of treatment efficacy. OBJECTIVES: We quantified specific features of focal embouchure dystonia using acoustic measures and developed a metric to assess severity across multiple domains of symptomatic impairment. METHODS: We recruited 9 brass musicians with and 6 without embouchure dystonia...
March 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Felix Carbonell, Yasser Iturria-Medina, Alan C Evans
Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood...
2018: Frontiers in Neurology
Shu-Ying Liu, Daryl J Wile, Jessie Fanglu Fu, Jason Valerio, Elham Shahinfard, Siobhan McCormick, Rostom Mabrouk, Nasim Vafai, Jess McKenzie, Nicole Neilson, Alexandra Perez-Soriano, Julieta E Arena, Mariya Cherkasova, Piu Chan, Jing Zhang, Cyrus P Zabetian, Jan O Aasly, Zbigniew K Wszolek, Martin J McKeown, Michael J Adam, Thomas J Ruth, Michael Schulzer, Vesna Sossi, A Jon Stoessl
BACKGROUND: Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease...
February 15, 2018: Lancet Neurology
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
Nicole K Polinski, Laura A Volpicelli-Daley, Caryl E Sortwell, Kelvin C Luk, Nunilo Cremades, Lindsey M Gottler, Jessica Froula, Megan F Duffy, Virginia M Lee, Terina N Martinez, Kuldip D Dave
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique new model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form-the aSyn pre-formed fibril (aSyn PFF)-which is then injected into the brain or introduced to the media in culture...
January 30, 2018: Journal of Parkinson's Disease
Davide L Vetrano, Maria S Pisciotta, Alice Laudisio, Maria R Lo Monaco, Graziano Onder, Vincenzo Brandi, Domenico Fusco, Beatrice Di Capua, Diego Ricciardi, Roberto Bernabei, Giuseppe Zuccalà
OBJECTIVES: In Parkinson disease (PD), sarcopenia may represent the common downstream pathway that from motor and nonmotor symptoms leads to the progressive loss of resilience, frailty, and disability. Here we (1) assessed the prevalence of sarcopenia in older adults with PD using 3 different criteria, testing their agreement, and (2) evaluated the association between PD severity and sarcopenia. DESIGN: Cross-sectional, observation study. SETTING: Geriatric day hospital...
January 30, 2018: Journal of the American Medical Directors Association
Orkid Coskuner-Weber, Vladimir N Uversky
Amyloid-β and α-synuclein are intrinsically disordered proteins (IDPs), which are at the center of Alzheimer's and Parkinson's disease pathologies, respectively. These IDPs are extremely flexible and do not adopt stable structures. Furthermore, both amyloid-β and α-synuclein can form toxic oligomers, amyloid fibrils and other type of aggregates in Alzheimer's and Parkinson's diseases. Experimentalists face challenges in investigating the structures and thermodynamic properties of these IDPs in their monomeric and oligomeric forms due to the rapid conformational changes, fast aggregation processes and strong solvent effects...
January 24, 2018: International Journal of Molecular Sciences
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
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
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...
February 1, 2018: JAMA Neurology
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...
January 2, 2018: Neurology
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 because of 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, 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...
January 19, 2018: Journal of Biological Chemistry
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
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
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...
December 11, 2017: Chemical Society Reviews
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...
February 26, 2018: Behavioural Brain Research
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
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
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