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Parkinson Disease: HELP
Articles from San Francisco Bay area
Based on 519 articles published since 2008
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These are the 519 published articles about Parkinson Disease that originated from San Francisco Bay area during 2008-2019.
 
+ 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 Mendel and urate: Acid test or random noise? 2018

Brown, Ethan G / Goldman, Samuel M / Tanner, Caroline M. ·Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Department of Neurology, Weil Institute for Neurosciences, University of California - San Francisco, San Francisco, CA, USA. · Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Division of Occupational and Environmental Medicine, University of California - San Francisco, San Francisco, CA, USA; Medical Service, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. · Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Department of Neurology, Weil Institute for Neurosciences, University of California - San Francisco, San Francisco, CA, USA; Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. Electronic address: Caroline.tanner@ucsf.edu. ·Parkinsonism Relat Disord · Pubmed #30100365.

ABSTRACT: -- No abstract --

2 Editorial Is pure autonomic failure an early marker for Parkinson disease, dementia with Lewy bodies, and multiple system atrophy? And other updates on recent autonomic research. 2017

Muppidi, Srikanth / Miglis, Mitchell G. ·Department of Neurology, Stanford Medical Center, 213 Quarry Road, 2nd Floor, Palo Alto, CA, 94304, USA. muppidis@stanford.edu. · Department of Neurology, Stanford Medical Center, 213 Quarry Road, 2nd Floor, Palo Alto, CA, 94304, USA. ·Clin Auton Res · Pubmed #28255741.

ABSTRACT: -- No abstract --

3 Editorial The sacral parasympathetic system is actually sympathetic-and other updates on recent autonomic research. 2017

Miglis, Mitchell G / Muppidi, Srikanth. ·Stanford Neurosciences Health Center, 213 Quarry Road, 2nd Floor, Palo Alto, CA, 94304, USA. · Stanford Neurosciences Health Center, 213 Quarry Road, 2nd Floor, Palo Alto, CA, 94304, USA. muppidis@stanford.edu. ·Clin Auton Res · Pubmed #28108826.

ABSTRACT: -- No abstract --

4 Editorial Role of Neuroinflammation in Parkinson Disease: The Enigma Continues. 2016

Mehta, Shyamal H / Tanner, Caroline M. ·Department of Neurology, Mayo Clinic, Scottsdale, AZ. Electronic address: mehta.shyamal@mayo.edu. · San Francisco Veterans Affairs Medical Center and Department of Neurology, University of California, San Francisco, CA. ·Mayo Clin Proc · Pubmed #27712631.

ABSTRACT: -- No abstract --

5 Editorial Electrophysiological insights into freezing in Parkinson's disease. 2016

Shine, James M. ·Department of Psychology, Stanford University, Stanford, CA, USA; Neuroscience Research Australia, The University of New South Wales, Sydney, NSW, Australia. Electronic address: macshine@stanford.edu. ·Clin Neurophysiol · Pubmed #27178847.

ABSTRACT: -- No abstract --

6 Editorial More than just a movement disorder: Why cognitive training is needed in Parkinson disease. 2015

Ventura, Maria I / Edwards, Jerri D / Barnes, Deborah E. ·From the Departments of Geriatrics (M.I.V.) and Psychiatry and Epidemiology & Statistics (D.E.B.), University of California, San Francisco · the School of Aging Studies (J.D.E.), University of South Florida, Tampa · and the San Francisco VA Medical Center (D.E.B.), San Francisco, CA. ·Neurology · Pubmed #26519546.

ABSTRACT: -- No abstract --

7 Editorial Commentary on "Adaptive deep brain stimulation in advanced Parkinson disease". 2013

Starr, Philip A / Ostrem, Jill L. ·Department of Neurosurgery, University of California, San Francisco, San Francisco, CA. ·Ann Neurol · Pubmed #23818322.

ABSTRACT: -- No abstract --

8 Review Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation. 2019

Kodani, Sean D / Morisseau, Christophe. ·Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA. · Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA. Electronic address: chmorisseau@ucdavis.edu. ·Biochimie · Pubmed #30716359.

ABSTRACT: Neuroinflammation is a physiologic response aimed at protecting the central nervous system during injury. However, unresolved and chronic neuroinflammation can lead to long term damage and eventually neurologic disease including Parkinson's disease, Alzheimer's disease and dementia. Recently, enhancing the concentration of epoxyeicosatrienoic acids (EETs) through blocking their hydrolytic degradation by soluble epoxide hydrolase (sEH) has been applied towards reducing the long-term damage associated with central neurologic insults. Evidence suggests this protective effect is mediated, at least in part, through polarization of microglia to an anti-inflammatory phenotype that blocks the inflammatory actions of prostaglandins and promotes wound repair. This mini-review overviews the epidemiologic basis for using sEH inhibition towards neuroinflammatory disease and pharmacologic studies testing sEH inhibition in several neurologic diseases. Additionally, the combination of sEH inhibition with other eicosanoid signaling pathways is considered as an enhanced approach for developing potent neuroprotectants.

9 Review LRRK2 and Rab GTPases. 2018

Pfeffer, Suzanne R. ·Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, U.S.A. pfeffer@stanford.edu. ·Biochem Soc Trans · Pubmed #30467121.

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is mutated in familial Parkinson's disease, and pathogenic mutations activate the kinase activity. A tour de force screen by Mann and Alessi and co-workers identified a subset of Rab GTPases as bona fide LRRK2 substrates. Rab GTPases are master regulators of membrane trafficking and this short review will summarize what we know about the connection between LRRK2 and this family of regulatory proteins. While, in most cases, Rab GTPase phosphorylation is predicted to interfere with Rab protein function, the discovery of proteins that show preferential binding to phosphorylated Rabs suggests that more complex interactions may also contribute to mutant LRRK2-mediated pathology.

10 Review Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences. 2018

de Andrade Teles, Roxana Braga / Diniz, Tâmara Coimbra / Costa Pinto, Tiago Coimbra / de Oliveira Júnior, Raimundo Gonçalves / Gama E Silva, Mariana / de Lavor, Érica Martins / Fernandes, Antonio Wilton Cavalcante / de Oliveira, Ana Paula / de Almeida Ribeiro, Fernanda Pires Rodrigues / da Silva, Amanda Alves Marcelino / Cavalcante, Taisy Cinthia Ferro / Quintans Júnior, Lucindo José / da Silva Almeida, Jackson Roberto Guedes. ·Postgraduate Program in Biotechnology, State University of Feira de Santana, 44036-900 Feira de Santana, BA, Brazil. · Federal University of San Francisco Valley, 56304-205 Petrolina, PE, Brazil. · Postgraduate Program in Neuropsychiatry and Behavioural Sciences, Federal University of Pernambuco, 50740-521 Recife, PE, Brazil. · UMRi CNRS 7266 LIENSs University of La Rochelle, La Rochelle, France. · University of Pernambuco, 56328-903 Petrolina, PE, Brazil. · Department of Physiology, Federal University of Sergipe, 49100-000 São Cristóvão, SE, Brazil. ·Oxid Med Cell Longev · Pubmed #29861833.

ABSTRACT: Alzheimer's and Parkinson's diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer's and Parkinson's diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer's disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson's disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

11 Review Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration. 2018

Quansah, Emmanuel / Peelaerts, Wouter / Langston, J William / Simon, David K / Colca, Jerry / Brundin, Patrik. ·Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. · KU Leuven, Laboratory for Gene Therapy and Neurobiology, 3000, Leuven, Belgium. · Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, CA, USA. · Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Metabolic Solutions Development Company, Kalamazoo, MI, 49007, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 333 Bostwick Ave, Michigan, 49503, USA. patrik.brundin@vai.org. ·Mol Neurodegener · Pubmed #29793507.

ABSTRACT: Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson's disease. Failure of cellular energy metabolism has long been implicated in sporadic Parkinson's disease and recent research on rare inherited forms of Parkinson's disease have added further weight to the importance of energy metabolism in the disease pathogenesis. There exists a new class of anti-diabetic insulin sensitizers in development that inhibit the mitochondrial pyruvate carrier (MPC), a protein which mediates the import of pyruvate across the inner membrane of mitochondria. Pharmacological inhibition of the MPC was recently found to be strongly neuroprotective in multiple neurotoxin-based and genetic models of neurodegeneration which are relevant to Parkinson's disease. In this review, we summarize the neuroprotective effects of MPC inhibition and discuss the potential putative underlying mechanisms. These mechanisms involve augmentation of autophagy via attenuation of the activity of the mammalian target of rapamycin (mTOR) in neurons, as well as the inhibition of neuroinflammation, which is at least partly mediated by direct inhibition of MPC in glia cells. We conclude that MPC is a novel and potentially powerful therapeutic target that warrants further study in attempts to slow Parkinson's disease progression.

12 Review Paradoxical Decision-Making: A Framework for Understanding Cognition in Parkinson's Disease. 2018

Perugini, Alessandra / Ditterich, Jochen / Shaikh, Aasef G / Knowlton, Barbara J / Basso, Michele A. ·Fuster Laboratory of Cognitive Neuroscience, Department of Psychiatry and Biobehavioral Sciences, Department of Neurobiology, Semel Institute for Neuroscience and Human Behavior, Brain Research Institute, The David Geffen School of Medicine, Los Angeles, CA 90095, USA. · Center for Neuroscience and Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA, USA. · Department of Neurology, Case Western Reserve University, Cleveland, OH 44106, USA. · Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA. · Fuster Laboratory of Cognitive Neuroscience, Department of Psychiatry and Biobehavioral Sciences, Department of Neurobiology, Semel Institute for Neuroscience and Human Behavior, Brain Research Institute, The David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: mbasso@mednet.ucla.edu. ·Trends Neurosci · Pubmed #29747856.

ABSTRACT: People with Parkinson's disease (PD) show impaired decision-making when sensory and memory information must be combined. This recently identified impairment results from an inability to accumulate the proper amount of information needed to make a decision and appears to be independent of dopamine tone and reinforcement learning mechanisms. Although considerable work focuses on PD and decisions involving risk and reward, in this Opinion article we propose that the emerging findings in perceptual decision-making highlight the multisystem nature of PD, and that unraveling the neuronal circuits underlying perceptual decision-making impairment may help in understanding other cognitive impairments in people with PD. We also discuss how a decision-making framework may be extended to gain insights into mechanisms of motor impairments in PD.

13 Review iPS cells in the study of PD molecular pathogenesis. 2018

Cobb, Melanie M / Ravisankar, Abinaya / Skibinski, Gaia / Finkbeiner, Steven. ·Gladstone Institutes, the Taube/Koret Center for Neurodegenerative Disease, San Francisco, CA, 94158, USA. · Gladstone Institutes, the Taube/Koret Center for Neurodegenerative Disease, San Francisco, CA, 94158, USA. steve.finkbeiner@gladstone.ucsf.edu. · Department of Neurology, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. · Department Physiology, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. · Graduate Programs in Neuroscience and Biomedical Sciences, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. ·Cell Tissue Res · Pubmed #29234887.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD. In this review, we describe how iPSCs have been used to improve our understanding of the pathogenesis of PD. We describe what cellular and molecular phenotypes have been observed in neurons derived from iPSCs harboring known PD-associated mutations and what common pathways may be involved.

14 Review Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review. 2018

Thevathasan, Wesley / Debu, Bettina / Aziz, Tipu / Bloem, Bastiaan R / Blahak, Christian / Butson, Christopher / Czernecki, Virginie / Foltynie, Thomas / Fraix, Valerie / Grabli, David / Joint, Carole / Lozano, Andres M / Okun, Michael S / Ostrem, Jill / Pavese, Nicola / Schrader, Christoph / Tai, Chun-Hwei / Krauss, Joachim K / Moro, Elena / Anonymous621156. ·Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia and the Bionics Institute of Australia, Melbourne, Australia. · Movement Disorders Center, Division of Neurology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble Alpes University, Grenoble, France. · Department of Neurosurgery, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Heidelberg, Germany. · Department of Bioengineering, Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, USA. · Department of Neurology, Institut de Cerveau et de la Moelle épinière, Sorbonne Universités, University Pierre-and-Marie-Curie (UPMC) Université, Paris, France. · Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, United Kingdom. · Department of Neurology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtière University Hospital, Paris, France. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders, Gainesville, Florida, USA. · Department of Neurology, UCSF Movement Disorder and Neuromodulation Center, University of California, San Francisco, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience, University of Aarhus, Aarhus, Denmark. · Department of Neurology, Hannover Medical School, Hannover, Germany. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Neurosurgery, Hannover Medical School, Hannover, Germany. ·Mov Disord · Pubmed #28960543.

ABSTRACT: Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

15 Review ER Stress and Neurodegenerative Disease: A Cause or Effect Relationship? 2018

Cabral-Miranda, Felipe / Hetz, Claudio. ·Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile. · Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile. · Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Independencia 1027, P.O.BOX 70086, Santiago, Chile. · Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. · Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile. chetz@med.uchile.cl. · Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile. chetz@med.uchile.cl. · Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Independencia 1027, P.O.BOX 70086, Santiago, Chile. chetz@med.uchile.cl. · Buck Institute for Research on Aging, Novato, CA, 94945, USA. chetz@med.uchile.cl. · Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, 02115, USA. chetz@med.uchile.cl. ·Curr Top Microbiol Immunol · Pubmed #28864830.

ABSTRACT: The accumulation of protein aggregates has a fundamental role in the patophysiology of distinct neurodegenerative diseases. This phenomenon may have a common origin, where disruption of intracellular mechanisms related to protein homeostasis (here termed proteostasis) control during aging may result in abnormal protein aggregation. The unfolded protein response (UPR) embodies a major element of the proteostasis network triggered by endoplasmic reticulum (ER) stress. Chronic ER stress may operate as possible mechanism of neurodegenerative and synaptic dysfunction, and in addition contribute to the abnormal aggregation of key disease-related proteins. In this article we overview the most recent findings suggesting a causal role of ER stress in neurodegenerative diseases.

16 Review Genetics of Synucleinopathies. 2018

Nussbaum, Robert L. ·Volunteer Clinical Faculty, UCSF School of Medicine, University of California, San Francisco, San Francisco, California 94143. ·Cold Spring Harb Perspect Med · Pubmed #28213435.

ABSTRACT: Parkinson's disease (PD), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA) constitute the three major neurodegenerative disorders referred to as synucleinopathies because both genetic and pathological results implicate the α-synuclein protein in their pathogenesis. PD and DLBD are recognized as closely related diseases with substantial clinical and pathological overlap. MSA, on the other hand, has a distinctive clinical presentation and neuropathological profile. In this review, we will summarize the evidence linking α-synuclein to these three disorders. Hundreds of patients with point or copy number mutations in the gene encoding α-synuclein,

17 Review Cell Biology and Pathophysiology of α-Synuclein. 2018

Burré, Jacqueline / Sharma, Manu / Südhof, Thomas C. ·Appel Institute for Alzheimer's Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021. · Departments of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305. · Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305. ·Cold Spring Harb Perspect Med · Pubmed #28108534.

ABSTRACT: α-Synuclein is an abundant neuronal protein that is highly enriched in presynaptic nerve terminals. Genetics and neuropathology studies link α-synuclein to Parkinson's disease (PD) and other neurodegenerative disorders. Accumulation of misfolded oligomers and larger aggregates of α-synuclein defines multiple neurodegenerative diseases called synucleinopathies, but the mechanisms by which α-synuclein acts in neurodegeneration are unknown. Moreover, the normal cellular function of α-synuclein remains debated. In this perspective, we review the structural characteristics of α-synuclein, its developmental expression pattern, its cellular and subcellular localization, and its function in neurons. We also discuss recent progress on secretion of α-synuclein, which may contribute to its interneuronal spread in a prion-like fashion, and describe the neurotoxic effects of α-synuclein that are thought to be responsible for its role in neurodegeneration.

18 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.

19 Review Neurodegenerative signaling factors and mechanisms in Parkinson's pathology. 2017

Goswami, Poonam / Joshi, Neeraj / Singh, Sarika. ·Neuronal Cell Death Mechanisms Laboratory, Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India. · Department of Biochemistry and Biophysics, Helen Diller Comprehensive Cancer Center, University of California San Francisco, USA. · Neuronal Cell Death Mechanisms Laboratory, Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India. Electronic address: sarika_singh@cdri.res.in. ·Toxicol In Vitro · Pubmed #28627426.

ABSTRACT: Parkinson's disease (PD) is a chronic and progressive degenerative disorder of central nervous system which is mainly characterized by selective loss of dopaminergic neurons in the nigrostrial pathway. Clinical symptoms of this devastating disease comprise motor impairments such as resting tremor, bradykinesia, postural instability and rigidity. Current medications only provide symptomatic relief but fail to halt the dopaminergic neuronal death. While the etiology of dopaminergic neuronal death is not fully understood, combination of various molecular mechanisms seems to play a critical role. Studies from experimental animal models have provided crucial insights into the molecular mechanisms in disease pathogenesis and recognized possible targets for therapeutic interventions. Recent findings implicate the involvement of abnormal protein accumulation and phosphorylation, mitochondrial dysfunction, oxidative damage and deregulated kinase signaling as key molecular mechanisms affecting the normal function as well survival of dopaminergic neurons. Here we discuss the relevant findings on the PD pathology related mechanisms and recognition of the cell survival mechanisms which could be used as targets for neuroprotective strategies in preventing this devastating disorder.

20 Review The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction. 2017

Zilberter, Yuri / Zilberter, Misha. ·Aix-Marseille Université, INSERM UMR1106, Institut de Neurosciences des Systèmes, Marseille, France. · Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, California, 94158, USA. ·J Neurosci Res · Pubmed #28463438.

ABSTRACT: Hypometabolism, characterized by decreased brain glucose consumption, is a common feature of many neurodegenerative diseases. Initial hypometabolic brain state, created by characteristic risk factors, may predispose the brain to acquired epilepsy and sporadic Alzheimer's and Parkinson's diseases, which are the focus of this review. Analysis of available data suggests that deficient glucose metabolism is likely a primary initiating factor for these diseases, and that resulting neuronal dysfunction further promotes the metabolic imbalance, establishing an effective positive feedback loop and a downward spiral of disease progression. Therefore, metabolic correction leading to the normalization of abnormalities in glucose metabolism may be an efficient tool to treat the neurological disorders by counteracting their primary pathological mechanisms. Published and preliminary experimental results on this approach for treating Alzheimer's disease and epilepsy models support the efficacy of metabolic correction, confirming the highly promising nature of the strategy. © 2017 Wiley Periodicals, Inc.

21 Review LRRK2 Phosphorylation. 2017

Nichols, R Jeremy. ·The Parkinson's Institute, Sunnyvale, CA, 94089, USA. jnichols@parkinsonsinstitute.org. ·Adv Neurobiol · Pubmed #28353278.

ABSTRACT: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene were discovered in 2004 and have been found to be the most frequently mutated gene in Parkinson's disease. LRRK2 is a large multi-domain protein with a functional GTPase and kinase domain. The signal transduction pathways in which LRRK2 is dysfunctional in the disease state are only now being resolved, but we do know that LRRK2 is, itself, a substrate of multiple kinases and phosphatases and exists in variable phosphorylated states. Autophosphorylation of LRRK2 can impact GTPase and pathological outcomes. LRRK2 serines (910/935/955/973) are differentially phosphorylated in pathogenic PD mutations and after LRRK2 kinase inhibition. The phosphorylation status of LRRK2 can therefore provide key insight into the mechanisms of kinase dysfunction during disease. This chapter will describe the identification of LRRK2 phosphorylation sites and how phosphoregulation of LRRK2 reveals its own kinase activity and regulates its ubiquitination and localization in vitro, in cells, and in tissues.

22 Review Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex. 2017

Xu, Tonghui / Wang, Shaofang / Lalchandani, Rupa R / Ding, Jun B. ·Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China. · Ministry of Education (MoE) Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, China. · Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, California, USA. · Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA. ·Mov Disord · Pubmed #28343366.

ABSTRACT: In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time-lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society.

23 Review Parkinson disease. 2017

Poewe, Werner / Seppi, Klaus / Tanner, Caroline M / Halliday, Glenda M / Brundin, Patrik / Volkmann, Jens / Schrag, Anette-Eleonore / Lang, Anthony E. ·Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. · Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, California, USA. · Department of Neurology, University of California - San Francisco, San Francisco, California, USA. · Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. · Faculty of Medicine, University of New South Wales &Neuroscience Research Australia, Sydney, New South Wales, Australia. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA. · Department of Neurology, University Hospital of Würzburg, Würzburg, Germany. · Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK. · Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. ·Nat Rev Dis Primers · Pubmed #28332488.

ABSTRACT: Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

24 Review A comprehensive overview of the neuropsychiatry of Parkinson's disease: A review. 2017

Khan, Muhammad Adnan / Quadri, Syed A / Tohid, Hassaan. ·Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. · Center for Mind & Brain, University of California, Davis. ·Bull Menninger Clin · Pubmed #28271905.

ABSTRACT: Parkinson's disease is a widespread neurological illness. However, its psychiatric links have also been discussed lately by many authors, which has brought more depth to the specialized field of neuropsychiatry. Neuropsychiatric complications are commonly seen in Parkinson's patients, including major depression, anxiety, psychosis and hallucination, and cognitive abnormality. Almost all of these complications have a distinct pathophysiology and treatment. In this article we review the most recent studies about the association of these symptoms with Parkinson's disease and highlight the epidemiology, diagnosis, pathophysiology, and treatment of the neuropsychiatric complications, with more emphasis on the pathophysiology of these complications.

25 Review A practical review of gastrointestinal manifestations in Parkinson's disease. 2017

Su, Andrew / Gandhy, Rita / Barlow, Carrolee / Triadafilopoulos, George. ·Medicine, Stanford University School of Medicine, Stanford, CA, United states; Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States. Electronic address: andrewmsu@gmail.com. · The Parkinson's Institute and Clinical Center, Sunnyvale, CA, United states. Electronic address: rgandhy@parkinsonsinstitute.org. · The Parkinson's Institute and Clinical Center, Sunnyvale, CA, United states. Electronic address: cbarlow@parkinsonsinstitute.org. · Medicine, Stanford University School of Medicine, Stanford, CA, United states; Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United states. Electronic address: vagt@stanford.edu. ·Parkinsonism Relat Disord · Pubmed #28258927.

ABSTRACT: Parkinson's disease (PD) is a chronic neurodegenerative disease with prominent motor and non-motor symptoms. Gastrointestinal (GI) dysfunction is among the most common and bothersome of non-motor symptoms that physicians will encounter while caring for their patients. Patients are subject to a wide variety of GI symptoms involving organs from the oropharynx to the anorectum. Our awareness and understanding of GI involvement in PD continues to evolve. In this review, we use a gastroenterologist's perspective to provide practical considerations for the diagnosis and symptom-based management of GI dysfunction seen in PD. Our aim is to assist neurologists and specialists as they encounter these symptoms while caring for the many neurologic manifestations of PD.

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