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Parkinson Disease: HELP
Articles from Illinois
Based on 524 articles published since 2009
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These are the 524 published articles about Parkinson Disease that originated from Illinois during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
1 Editorial Cerebrospinal fluid levels of alpha-synuclein in PARKINSON'S disease: Another long and winding road. 2018

Markopoulou, Katerina / Compta, Yaroslau. ·Movement Disorders Section, Department of Neurology, NorthShore University HealthSystem, Chicago, Evanston, USA; University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, Barcelona, Catalonia, Spain; Physiology Unit, Department of Biomedicine, Institut de Neurociències, University of Barcelona, Barcelona, Catalonia, Spain. Electronic address: ycompta@clinic.cat. ·Parkinsonism Relat Disord · Pubmed #29548634.

ABSTRACT: -- No abstract --

2 Editorial Closing the celebration of 200 years of Parkinson's Essay on the Shaking Palsy: Where do we go in the next 200 years? 2017

Goetz, Christopher G. ·Rush University Medical Center, Chicago, Illinois, USA. ·Mov Disord · Pubmed #29119602.

ABSTRACT: -- No abstract --

3 Editorial Virtually reducing fall risk in Parkinson disease. 2017

Moreau, Caroline / Barton, Brandon R / Devos, David. ·From the Service de Neurologie (C.M., D.D.) and Services de Pharmacologie and Médicale (D.D.), LICEND COEN Center, Université de Lille, CHU de Lille, INSERM UMRS_1171, France · Department of Neurological Sciences (B.R.B.), Rush University Medical Center · and Neurology Service (B.R.B.), Jesse Brown VA Medical Center, Chicago, IL. ·Neurology · Pubmed #28954881.

ABSTRACT: -- No abstract --

4 Editorial What would Dr. James Parkinson think today? parcelling out the circuitry of levodopa-induced dyskinesias. 2017

Kordower, Jeffrey H. ·Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, 60612. · The Van Andel Research Institute, Grand Rapids Michigan, 49503. ·Mov Disord · Pubmed #28425143.

ABSTRACT: -- No abstract --

5 Editorial Fetal grafts for Parkinson's disease: Decades in the making. 2016

Kordower, Jeffrey H / Olanow, C Warren. ·Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612; Van Andel Institute, Grand Rapids, MI 49503; jkordowe@rush.edu. · Department of Neurology, Mt. Sinai School of Medicine, New York, NY 10029; Department of Neuroscience, Mt. Sinai School of Medicine, New York, NY 10029. ·Proc Natl Acad Sci U S A · Pubmed #27247420.

ABSTRACT: -- No abstract --

6 Editorial Preface. 2015

Poewe, Werner / Goetz, Christopher G. ·Innsbruck Medical University, Austria. · Rush University Medical Center, Chicago, Illinois. ·Mov Disord · Pubmed #26301896.

ABSTRACT: -- No abstract --

7 Review Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson's Disease. 2019

Nguyen, Maria / Wong, Yvette C / Ysselstein, Daniel / Severino, Alex / Krainc, Dimitri. ·Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. · Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: dkrainc@nm.org. ·Trends Neurosci · Pubmed #30509690.

ABSTRACT: The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1), have also highlighted disruptions in synaptic vesicle endocytosis (SVE) as a significant contributor to disease pathogenesis. Additionally, the roles of other PD genes such as LRRK2, PRKN, and VPS35 in the regulation of SVE are beginning to emerge. Here we discuss the recent work on the contribution of dysfunctional SVE to midbrain dopaminergic neurons' selective vulnerability and highlight pathways that demonstrate the interplay of synaptic, mitochondrial, and lysosomal dysfunction in the pathogenesis of PD.

8 Review What influences placebo and nocebo responses in Parkinson's disease? 2018

Witek, Natalie / Stebbins, Glenn T / Goetz, Christopher G. ·Rush Parkinson's Disease and Movement Disorders Program, Chicago, Illinois, USA. ·Mov Disord · Pubmed #30132980.

ABSTRACT: Placebo treatment is associated with clinical improvements in many medical conditions, but is particularly important in Parkinson's disease because improvements are common, marked, and associated with objective neurochemical and neurophysiologic changes. This review will focus on the effect of the placebo in patients with PD and will discuss the pathophysiology, observed characteristics of motor and nonmotor placebo responses, and the patient and study characteristics that modify the placebo response. Similar to the placebo response, nocebo and lessebo effects alter clinical trial outcomes and impact conclusions. Whereas placebo-associated improvements are positively viewed by patients in clinical practice, they complicate clinical trials. The authors suggest strategies to reduce placebo effects during randomized placebo-controlled trials evaluating new therapies. © 2018 International Parkinson and Movement Disorder Society.

9 Review Determinants of dopaminergic neuron loss in Parkinson's disease. 2018

Surmeier, Dalton James. ·Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. ·FEBS J · Pubmed #30028088.

ABSTRACT: The cardinal motor symptoms of Parkinson's disease (PD) are caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Alpha-synuclein (aSYN) pathology and mitochondrial dysfunction have been implicated in PD pathogenesis, but until recently it was unclear why SNc dopaminergic neurons should be particularly vulnerable to these two types of insult. In this brief review, the evidence that SNc dopaminergic neurons have an anatomical, physiological, and biochemical phenotype that predisposes them to mitochondrial dysfunction and synuclein pathology is summarized. The recognition that certain traits may predispose neurons to PD-linked pathology creates translational opportunities for slowing or stopping disease progression.

10 Review Disease Modification for Parkinson's Disease: Axonal Regeneration and Trophic Factors. 2018

Kordower, Jeffrey H / Burke, Robert E. ·Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Van Andel Research Institute, Grand Rapids, Michigan, USA. · Department of Neurology, Columbia University, New York, New York, USA. · Department of Pathology and Cell Biology, Columbia University, New York, New York, USA. ·Mov Disord · Pubmed #29603370.

ABSTRACT: Disease modification and structural neuroprotection have been the holy grail for Parkinson's disease (PD) experimental therapeutics. Theoretically, there are a number of ways to implement such therapeutics, but to date all have failed. This review examines the potential of axonal regeneration and trophic factor delivery for the nigrostriatal system as 2 such approaches that historically have initiated much excitement. However, we conclude this discussion with the following question: has science passed these approaches by? © 2018 International Parkinson and Movement Disorder Society.

11 Review International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. 2018

Fox, Susan H / Katzenschlager, Regina / Lim, Shen-Yang / Barton, Brandon / de Bie, Rob M A / Seppi, Klaus / Coelho, Miguel / Sampaio, Cristina / Anonymous1591441. ·Edmund J. Safra Program, Movement Disorder Clinic, Toronto Western Hospital, Toronto, Ontario, Canada. · University of Toronto Department of Medicine, Toronto, Ontario, Canada. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital, Vienna, Austria. · Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, University of Malaya, Kuala Lumpur, Malaysia. · Rush University Medical Center, Chicago, Illinois, USA. · Jesse Brown VA Medical Center, Chicago, Illinois, USA. · Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Santa Maria Hospital, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal. · Cure Huntington's Disease Initiative (CHDI) Management/CHDI Foundation, Princeton, NJ, USA. · Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal. ·Mov Disord · Pubmed #29570866.

ABSTRACT: OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

12 Review Initial cognitive changes in Parkinson's disease. 2018

Weintraub, Daniel / Tröster, Alexander I / Marras, Connie / Stebbins, Glenn. ·Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia, Pennsylvania, USA. · Barrow Neurological Institute, Department of Clinical Neuropsychology and Barrow Center for Neuromodulation, Phoenix, Arizona, USA. · Department of Neurology, University of Toronto, Toronto, Ontario, Canada. · Rush University Medical Center, Department of Neurological Sciences, Chicago, Illinois, USA. ·Mov Disord · Pubmed #29543342.

ABSTRACT: The focus on cognitive impairment in neurodegenerative diseases, including PD, is shifting from the dementia stage to earlier stages of impairment, including mild cognitive impairment. This shift is driven primarily by the desire to improve long-term outcomes by delivering therapeutic interventions earlier in the clinical course, even presymptomatically in those at highest risk, and at the initial stage in the pathophysiological cascade that underpins common dementia syndromes. This article focuses on key findings and challenges in studying earliest stages of cognitive decline in PD, including a detailed examination of neuropsychological testing, cognitive performance in early and prodromal PD, epidemiological research for PD mild cognitive impairment to date, and expert recommendations for assessment. © 2018 International Parkinson and Movement Disorder Society.

13 Review Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment. 2018

Goldman, Jennifer G / Holden, Samantha K / Litvan, Irene / McKeith, Ian / Stebbins, Glenn T / Taylor, John-Paul. ·Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, University of Colorado, Department of Neurology, Aurora, Colorado, USA. · Department of Neurosciences, University of California San Diego, Department of Neurosciences, San Diego, California, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom. ·Mov Disord · Pubmed #29488270.

ABSTRACT: Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society.

14 Review The spectrum of "off" in Parkinson's disease: What have we learned over 40 years? 2018

Chou, Kelvin L / Stacy, Mark / Simuni, Tanya / Miyasaki, Janis / Oertel, Wolfgang H / Sethi, Kapil / Fernandez, Hubert H / Stocchi, Fabrizio. ·Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: klchou@med.umich.edu. · Department of Neurology, Duke University Medical Center, Durham, NC, USA. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Division of Neurology, Department of Medicine, University of Alberta, Kaye Edmonton Clinic, Canada. · Department of Neurology, University Clinic, Philipps Universität Marburg, Marburg, Germany; Institute for Neurogenomics, Helmholtz Center for Health and Environment, Munich, Germany. · Department of Neurology, Medical College of Georgia at Augusta University, Augusta, GA, USA. · Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA. · Department of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele Roma, Roma, Italy. ·Parkinsonism Relat Disord · Pubmed #29456046.

ABSTRACT: The terms "on" and "off" were used by Marsden and his contemporaries over 40 years ago to describe times when Parkinson's disease patients experienced good motor function ("on") and immobility ("off"). Yet there remains no published consensus definition of "off", leading clinicians and patients to develop individualized impressions of "off" determinations. In this paper, we first discuss the evolution of the terminology and understanding of "off" states since Marsden's time, which now include non-motor as well as motor symptoms. We then review pathophysiology and risk factors for the development of "off" states as well as tools to detect the "off" state, before proposing a practical definition of "off" for consideration. A common, practical definition of the "off" state could improve clinical recognition of "off" symptoms and lead to significant benefit for patients.

15 Review Global scales for cognitive screening in Parkinson's disease: Critique and recommendations. 2018

Skorvanek, Matej / Goldman, Jennifer G / Jahanshahi, Marjan / Marras, Connie / Rektorova, Irena / Schmand, Ben / van Duijn, Erik / Goetz, Christopher G / Weintraub, Daniel / Stebbins, Glenn T / Martinez-Martin, Pablo / Anonymous2421195. ·Department of Neurology, Safarik University, Kosice, Slovakia. · Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovakia. · Rush University Medical Center, Department of Neurological Sciences, Section of Parkinson Disease and Movement Disorders, Chicago, Illinois, USA. · Sobell Department of Motor Neuroscience & Movement Disorders and the National Hospital for Neurology & Neurosurgery, London, UK. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Ontario, Canada. · Applied Neuroscience Research Group, Central European Institute of Technology, CEITEC, Masaryk University, Brno, Czech Republic. · Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, Leiden University Medical Centre, Leiden, and Centre of Mental Health Care Delfland, Delft, Netherlands. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania and Parkinson's Disease and Mental Health Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. · National Centre of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #29168899.

ABSTRACT: BACKGROUND: Cognitive impairment is a common nonmotor manifestation of Parkinson's disease, with deficits ranging from mild cognitive difficulties in 1 or more of the cognitive domains to severe dementia. The International Parkinson and Movement Disorder Society commissioned the assessment of the clinimetric properties of cognitive rating scales measuring global cognitive performance in PD to make recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the scales used to assess global cognitive performance in PD, and the identified scales were reviewed and rated as "recommended," "recommended with caveats," "suggested," or "listed" by the panel using previously established criteria. RESULTS: A total of 12 cognitive scales were included in this review. Three scales, the Montreal Cognitive Assessment, the Mattis Dementia Rating Scale Second Edition, and the Parkinson's Disease-Cognitive Rating Scale, were classified as "recommended." Two scales were classified as "recommended with caveats": the Mini-Mental Parkinson, because of limited coverage of executive abilities, and the Scales for Outcomes in Parkinson's Disease-Cognition, which has limited data on sensitivity to change. Six other scales were classified as "suggested" and 1 scale as "listed." CONCLUSIONS: Because of the existence of "recommended" scales for assessment of global cognitive performance in PD, this task force suggests that the development of a new scale for this purpose is not needed at this time. However, global cognitive scales are not a substitute for comprehensive neuropsychological testing. © 2017 International Parkinson and Movement Disorder Society.

16 Review Molecular mechanisms of α-synuclein and GBA1 in Parkinson's disease. 2018

Stojkovska, Iva / Krainc, Dimitri / Mazzulli, Joseph R. ·The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Ward 12-369, Chicago, IL, 60611, USA. · The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Ward 12-369, Chicago, IL, 60611, USA. jmazzulli@northwestern.edu. ·Cell Tissue Res · Pubmed #29064079.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative movement disorder characterized pathologically by the presence of Lewy bodies comprised of insoluble alpha (α)-synuclein. Pathological, clinical and genetic studies demonstrate that mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase) that is deficient in Gaucher's disease, are important risk factors for the development of PD. The molecular mechanism for the association between these two diseases is not completely understood. We discuss several possible mechanisms that may lead to GBA1-related neuronal death and α-synuclein accumulation including disruptions in lipid metabolism, protein trafficking and impaired protein quality control mechanisms. Elucidating the mechanism between GCase and α-synuclein may provide insight into potential therapeutic pathways for PD and related synucleinopathies.

17 Review Striatal synapses, circuits, and Parkinson's disease. 2018

Zhai, Shenyu / Tanimura, Asami / Graves, Steven M / Shen, Weixing / Surmeier, D James. ·Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: j-surmeier@northwestern.edu. ·Curr Opin Neurobiol · Pubmed #28843800.

ABSTRACT: The striatum is a hub in the basal ganglia circuitry controlling goal directed actions and habits. The loss of its dopaminergic (DAergic) innervation in Parkinson's disease (PD) disrupts the ability of the two principal striatal projection systems to respond appropriately to cortical and thalamic signals, resulting in the hypokinetic features of the disease. New tools to study brain circuitry have led to significant advances in our understanding of striatal circuits and how they adapt in PD models. This short review summarizes some of these recent studies and the gaps that remain to be filled.

18 Review Falls in Parkinson's disease: A complex and evolving picture. 2017

Fasano, Alfonso / Canning, Colleen G / Hausdorff, Jeffrey M / Lord, Sue / Rochester, Lynn. ·Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada. · Krembil Research Institute, Toronto, Ontario, Canada. · Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Sydney, Australia. · Center for Study of Movement, Cognition and Mobility, Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Sagol School of Neuroscience and Department of Physical Therapy, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. · Rush Alzheimer's Disease Center and Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, US. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Auckland University of Technology, Auckland, New Zealand. · Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne, UK. ·Mov Disord · Pubmed #29067726.

ABSTRACT: Falls are a major determinant of poor quality of life, immobilization, and reduced life expectancy in people affected by Parkinson's disease (PD) and in older adults more generally. Although many questions remain, recent research has advanced the understanding of this complex problem. The goal of this review is to condense new knowledge of falls in PD from prodromal to advanced disease, taking into account risk factors, assessment, and classification as well as treatment. The fundamental steps of clinical and research-based approaches to falls are described, namely, the identification of fall risk factors, clinical and instrumental methods to evaluate and classify fall risk, and the latest evidence to reduce or delay falls in PD. We summarize recent developments, the direction in which the field should be heading, and what can be recommended at this stage. We also provide a practical algorithm for clinicians.© 2017 International Parkinson and Movement Disorder Society.

19 Review Parkinson's Disease Is Not Simply a Prion Disorder. 2017

Surmeier, D James / Obeso, José A / Halliday, Glenda M. ·Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, j-surmeier@northwestern.edu. · CINAC, HM Puerta del Sur, Hospitales de Madrid, Mostoles and CEU-San Pablo University, 28938 Madrid, Spain. · Network Center for Biomedical Research on Neurodegenerative Diseases, Instituto Carlos III, 28029 Madrid, Spain. · Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, 2006 New South Wales, Australia, and. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, 2052 New South Wales, Australia. ·J Neurosci · Pubmed #29021297.

ABSTRACT: The notion that prion-like spreading of misfolded α-synuclein (α-SYN) causes Parkinson's disease (PD) has received a great deal of attention. Although attractive in its simplicity, the hypothesis is difficult to reconcile with postmortem analysis of human brains and connectome-mapping studies. An alternative hypothesis is that PD pathology is governed by regional or cell-autonomous factors. Although these factors provide an explanation for the pattern of neuronal loss in PD, they do not readily explain the apparently staged distribution of Lewy pathology in many PD brains, the feature of the disease that initially motivated the spreading hypothesis by Braak and colleagues. While each hypothesis alone has its shortcomings, a synthesis of the two can explain much of what we know about the etiopathology of PD.

20 Review Therapeutic approaches to target alpha-synuclein pathology. 2017

Brundin, Patrik / Dave, Kuldip D / Kordower, Jeffrey H. ·Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA. Electronic address: Patrik.Brundin@vai.org. · The Michael J Fox Foundation, New York, NY 10017, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA. ·Exp Neurol · Pubmed #28987463.

ABSTRACT: Starting two decades ago with the discoveries of genetic links between alpha-synuclein and Parkinson's disease risk and the identification of aggregated alpha-synuclein as the main protein constituent of Lewy pathology, alpha-synuclein has emerged as the major therapeutic target in Parkinson's disease and related synucleinopathies. Following the suggestion that alpha-synuclein pathology gradually spreads through the nervous system following a stereotypic pattern and the discovery that aggregated forms of alpha-synuclein can propagate pathology from one cell to another, and thereby probably aggravate existing deficits as well as generate additional symptoms, the idea that alpha-synuclein is a viable therapeutic target gained further support. In this review we describe current challenges and possibilities with alpha-synuclein as a therapeutic target. We briefly highlight gaps in the knowledge of the role of alpha-synuclein in disease, and propose that a deeper understanding of the pathobiology of alpha-synuclein can lead to improved therapeutic strategies. We describe several treatment approaches that are currently being tested in advanced animal experiments or already are in clinical trials. We have divided them into approaches that reduce alpha-synuclein production; inhibit alpha-synuclein aggregation inside cells; promote its degradation either inside or outside cells; and reduce its uptake by neighbouring cells following release from already affected neurons. Finally, we briefly discuss challenges related to the clinical testing of alpha-synuclein therapies, for example difficulties in monitoring target engagement and the need for relatively large trials of long duration. We conclude that alpha-synuclein remains one of the most compelling therapeutic targets for Parkinson's disease, and related synucleinopathies, and that the multitude of approaches being tested provides hope for the future.

21 Review Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson's Disease. 2017

Padovan-Neto, Fernando E / West, Anthony R. ·Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA. fernando.padovanneto@rosalindfranklin.edu. · Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL, 60064, USA. anthony.west@rosalindfranklin.edu. ·Adv Neurobiol · Pubmed #28956336.

ABSTRACT: Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in the brain. Several classes of PDE enzymes with distinct tissue distributions, cyclic nucleotide selectivity, and regulatory factors are highly expressed in brain regions subserving cognitive and motor processes known to be disrupted in neurodegenerative diseases such as Parkinson's disease (PD). Furthermore, small-molecule inhibitors of several different PDE family members alter cyclic nucleotide levels and favorably enhance motor performance and cognition in animal disease models. This chapter will explore the roles and therapeutic potential of non-selective and selective PDE inhibitors on neural processing in fronto-striatal circuits in normal animals and models of DOPA-induced dyskinesias (LIDs) associated with PD. The impact of selective PDE inhibitors and augmentation of cAMP and cGMP signaling on the membrane excitability of striatal medium-sized spiny projection neurons (MSNs) will be discussed. The effects of cyclic nucleotide signaling and PDE inhibitors on synaptic plasticity of striatonigral and striatopallidal MSNs will be also be reviewed. New data on the efficacy of PDE10A inhibitors for reversing behavioral and electrophysiological correlates of L-DOPA-induced dyskinesias in a rat model of PD will also be presented. Together, these data will highlight the potential of novel PDE inhibitors for treatment of movement disorders such as PD which are associated with abnormal corticostriatal transmission.

22 Review Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. 2017

Obeso, J A / Stamelou, M / Goetz, C G / Poewe, W / Lang, A E / Weintraub, D / Burn, D / Halliday, G M / Bezard, E / Przedborski, S / Lehericy, S / Brooks, D J / Rothwell, J C / Hallett, M / DeLong, M R / Marras, C / Tanner, C M / Ross, G W / Langston, J W / Klein, C / Bonifati, V / Jankovic, J / Lozano, A M / Deuschl, G / Bergman, H / Tolosa, E / Rodriguez-Violante, M / Fahn, S / Postuma, R B / Berg, D / Marek, K / Standaert, D G / Surmeier, D J / Olanow, C W / Kordower, J H / Calabresi, P / Schapira, A H V / Stoessl, A J. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles, Madrid, Spain. · Universidad CEU San Pablo, Madrid, Spain. · CIBERNED, Madrid, Spain. · Department of Neurology, Philipps University, Marburg, Germany. · Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital and Attikon Hospital, University of Athens, Athens, Greece. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · Department of Medicine, University of Toronto, Toronto, Canada. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Corporal Michael J. Crescenz Veteran's Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Medical Sciences, Newcastle University, Newcastle, UK. · Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, Australia. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · China Academy of Medical Sciences, Institute of Lab Animal Sciences, Beijing, China. · Departments of Neurology, Pathology, and Cell Biology, the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA. · Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA. · Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Clinical Sciences Department, Newcastle University, Newcastle, UK. · Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark. · Human Neurophysiology, Sobell Department, UCL Institute of Neurology, London, UK. · Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Movement Disorders and Neuromodulation Center, Department of Neurology, University of California-San Francisco, San Francisco, California, USA. · Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA. · Parkinson's Institute, Sunnyvale, California, USA. · Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Department of Neurology, Universitätsklinikum Schleswig-Holstein, Christian Albrechts University Kiel, Kiel, Germany. · Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem, Israel. · Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel. · Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Medicine, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Barcelona, Spain. · Movement Disorders Clinic, Clinical Neurodegenerative Research Unit, Mexico City, Mexico. · Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. · Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Graduate Program, Rush University Medical Center, Chicago, Illinois, USA. · Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy. · University Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, UK. · Pacific Parkinson's Research Centre, Division of Neurology & Djavadf Mowafaghian Centre for Brain Health, University of British Columbia, British Columbia, Canada. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #28887905.

ABSTRACT: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

23 Review Pimavanserin, a novel antipsychotic for management of Parkinson's disease psychosis. 2017

Kianirad, Yasaman / Simuni, Tanya. ·a Department of Neurology , Northwestern University, Feinberg School of Medicine , Chicago , IL , USA. ·Expert Rev Clin Pharmacol · Pubmed #28817967.

ABSTRACT: INTRODUCTION: Parkinson's disease psychosis (PDP) may develop in up to 60% of Parkinson's patients and is associated with increased morbidity and mortality. It also correlates with depression and dementia, and can contribute to caregiver stress and burnout. Pimavanserin is the first FDA approved drug for the treatment of hallucinations and delusions associated with PDP. Areas covered: For this review, a MEDLINE literature search (via PubMed) and information provided by ACADIA Pharmaceuticals were used. This review will discuss the pathophysiology and current management of PDP. In addition, this review will focus on the rationales behind the development of pimavanserin, mechanism of action, pharmacokinetics, pharmacodynamics, and the clinical trials evaluating the efficacy and safety of pimavanserin. Last, the review will address the drug's package insert warning. Expert commentary: Pimavanserin, a 5HT2A receptor inverse agonist, is the first FDA approved drug for the treatment of PDP which has been shown to reduce psychosis in PD through its unique mechanism of action. Pimavanserin, does not worsen PD motor symptoms and has an acceptable safety profile. The development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease.

24 Review Calcium, mitochondrial dysfunction and slowing the progression of Parkinson's disease. 2017

Surmeier, D James / Halliday, Glenda M / Simuni, Tanya. ·Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: j-surmeier@northwestern.edu. · Brain and Mind Centre, Sydney Medical School, University of Sydney, 2006, Australia; School of Medical Sciences, University of New South Wales, Neuroscience Research Australia, Sydney 2052, Australia. · Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. ·Exp Neurol · Pubmed #28780195.

ABSTRACT: Parkinson's disease is characterized by progressively distributed Lewy pathology and neurodegeneration. The motor symptoms of clinical Parkinson's disease (cPD) are unequivocally linked to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several features of these neurons appear to make them selectively vulnerable to factors thought to cause cPD, like aging, genetic mutations and environmental toxins. Among these features, Ca

25 Review A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations. 2017

Mollenhauer, Brit / Batrla, Richard / El-Agnaf, Omar / Galasko, Douglas R / Lashuel, Hilal A / Merchant, Kalpana M / Shaw, Lesley M / Selkoe, Dennis J / Umek, Robert / Vanderstichele, Hugo / Zetterberg, Henrik / Zhang, Jing / Caspell-Garcia, Chelsea / Coffey, Chris / Hutten, Samantha J / Frasier, Mark / Taylor, Peggy / Anonymous5870913. ·Paracelsus-Elena-Klinik, Kassel, Germany. · Department of Neurology, University Medical Center, Göttingen, Germany. · Roche Diagnostics International Ltd, Rotkreuz, Switzerland. · Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), and College of Science and Engineering, HBKU, Education City, Qatar Foundation, Doha, Qatar. · University of San Diego, San Diego, California, USA. · Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Faculty of Life Science, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland. · Northwestern University School of Medicine, Chicago, Illinois, USA. · Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Center for Neurodegenerative Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · MesoScale Discovery, Gaithersburg, Maryland, USA. · ADx NeuroSciences, Gent, Belgium. · Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK. · University of Washington, Seattle, Washington, USA. · Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA. · Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA. · BioLegend, Dedham, Massachusetts, USA. ·Mov Disord · Pubmed #28734051.

ABSTRACT: 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. We also discuss analytical confounders. We identify gaps in the knowledge and delineate specific areas that require further investigation, such as the need to identify posttranslational modifications of α-synuclein and antibody-independent reference methods for quantification, as well as the analysis of potential confounders, such as comorbidities, medication, and phenotypes of Parkinson's disease in larger cohorts. This review could be used as a guideline for future Parkinson's disease biomarker studies and will require regular updating as more information arises in this growing field, including new technical developments as they become available. In addition to reviewing best practices, we also identify the current technical limitations and gaps in the knowledge that should be addressed to enable accurate and quantitative assessment of α-synuclein levels in the clinical setting. © 2017 International Parkinson and Movement Disorder Society.

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