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Parkinson Disease: HELP
Articles from Columbia University
Based on 251 articles published since 2008
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These are the 251 published articles about Parkinson Disease that originated from Columbia University during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11
1 Editorial Cytokines as Potential Biomarkers of Parkinson Disease. 2016

Alcalay, Roy N. ·Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York2Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York. ·JAMA Neurol · Pubmed #27669063.

ABSTRACT: -- No abstract --

2 Editorial Advances in Experimental Neuropathology: New Methods and Insights. 2016

Roth, Kevin A. ·Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York. Electronic address: karoth@columbia.edu. ·Am J Pathol · Pubmed #26802320.

ABSTRACT: This Editorial introduces this month's special Neuropathology Theme Issue, a series of Reviews on advances in our understanding of rare human hereditary neuropathies, peripheral nervous system tumors, and common degenerative diseases.

3 Editorial Milk consumption and the risk of nigral degeneration. 2016

Chen, Honglei / Marder, Karen. ·From the Epidemiology Branch (H.C.), National Institute of Environmental Health Sciences, Research Triangle Park, NC · and the Department of Neurology (K.M.), College of Physicians and Surgeons, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY. ·Neurology · Pubmed #26658908.

ABSTRACT: -- No abstract --

4 Editorial Levodopa: 50 years of a revolutionary drug for Parkinson disease. 2015

Fahn, Stanley / Poewe, Werner. ·Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY, 10032, U.S.A. ·Mov Disord · Pubmed #25488146.

ABSTRACT: -- No abstract --

5 Editorial A critical evaluation of the Braak staging scheme for Parkinson's disease. 2008

Burke, Robert E / Dauer, William T / Vonsattel, Jean Paul G. ·Department of Neurology, Columbia University Medical Center, New York, NY, USA. rb43@columbia.edu ·Ann Neurol · Pubmed #19067353.

ABSTRACT: Braak and colleagues have proposed that, within the central nervous system, Parkinson's disease (PD) begins as a synucleinopathy in nondopaminergic structures of the lower brainstem or in the olfactory bulb. The brainstem synucleinopathy is postulated to progress rostrally to affect the substantia nigra and cause parkinsonism at a later stage of the disease. In the context of a diagnosis of PD, made from current clinical criteria, the pattern of lower brainstem involvement accompanying mesencephalic synucleinopathy is often observed. However, outside of that context, the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations. The concept that lower brainstem synucleinopathy represents "early PD" rests on the supposition that it has a substantial likelihood of progressing within the human lifetime to involve the mesencephalon, and thereby cause the substantia nigra pathology and clinical parkinsonism that have heretofore defined the disease. However, the predictive validity of this concept is doubtful, based on numerous observations made in populations of aged individuals who, despite the absence of neurological signs, have brain synucleinopathy ranging up to Braak stages 4 to 6 at postmortem. Furthermore, there is no relation between Braak stage and the clinical severity of PD. We conclude that the relation between patterns of abnormal synuclein immunostaining in the human brain and the disease entity now recognized as PD remains to be determined.

6 Review Sleep disorders and Parkinson disease; lessons from genetics. 2018

Gan-Or, Ziv / Alcalay, Roy N / Rouleau, Guy A / Postuma, Ronald B. ·Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. · Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. · Montreal Neurological Institute, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. · Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. ·Sleep Med Rev · Pubmed #29449121.

ABSTRACT: Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment.

7 Review Induction of axon growth in the adult brain: A new approach to restoration in Parkinson's disease. 2018

Padmanabhan, Shalini / Burke, Robert E. ·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 #29205486.

ABSTRACT: -- No abstract --

8 Review Synaptic plasticity may underlie l-DOPA induced dyskinesia. 2018

Borgkvist, Anders / Lieberman, Ori J / Sulzer, David. ·Departments of Neurology, Columbia University Medical Center and Division of Molecular Therapeutics, New York State Psychiatric Institute, United States. Electronic address: ab3380@cumc.columbia.edu. · Departments of Psychiatry, Pharmacology, Columbia University Medical Center and Division of Molecular Therapeutics, New York State Psychiatric Institute, United States. ·Curr Opin Neurobiol · Pubmed #29125979.

ABSTRACT: l-DOPA provides highly effective treatment for Parkinson's disease, but l-DOPA induced dyskinesia (LID) is a very debilitating response that eventually is presented by a majority of patients. A central issue in understanding the basis of LID is whether it is due to a response to chronic l-DOPA over years of therapy, and/or due to synaptic changes that follow the loss of dopaminergic neurotransmission and then triggered by acute l-DOPA administration. We review recent work that suggests that specific synaptic changes in the D1 dopamine receptor-expressing direct pathway striatal projection neurons due to loss of dopamine in Parkinson's disease are responsible for LID. Chronic l-DOPA may nevertheless modulate LID through priming mechanisms.

9 Review The 200-year journey of Parkinson disease: Reflecting on the past and looking towards the future. 2018

Fahn, Stanley. ·Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA. Electronic address: sf1@columbia.edu. ·Parkinsonism Relat Disord · Pubmed #28784297.

ABSTRACT: It took almost 100 years before a meaningful advance occurred in any basic science understanding of Parkinson disease (PD) following James Parkinson's description in 1817. The Lewy body was described in 1912, and the substantia nigra was found to be depigmented with neuronal loss and gliosis in 1919. The link between dopamine and PD began in 1957, 140 years after Parkinson's Essay. Arvid Carlsson and Oleh Hornykiewicz were the major pioneers. The revolutionary therapeutic breakthrough was the introduction of high dosage levodopa therapy by George Cotzias in 1967. Following 40 years of the dopa/dopamine era, we have entered the era of alpha-synuclein, the protein present in Lewy bodies. Heiko Braak found that alpha-synuclein accumulates initially in the olfactory system and lower brainstem and then travels in an anatomic pattern to involve other regions of the brain and thereby cause progressive symptoms. Alpha-synuclein was somehow converted to a rogue protein. Where this originates and how it is propagated are under intense investigation. At the same time that the alpha-synuclein era was developing, clinical advances took place by recognizing PD as hosting a wide variety of nonmotor features with eventual cognitive impairment in many. Therapeutics has also evolved. Although the most effective therapy for the motor features remains levodopa, surgical approaches and drugs for nonmotor problems continue to expand our ability to treat people with PD. We can expect therapeutic advances in neuroprotection as the basic science discoveries uncovered in the alpha-synuclein era are translated into effective treatments.

10 Review Two-hundred Years Later: Is Parkinson's Disease a Single Defined Entity? 2017

Rodríguez-Violante, Mayela / Cervantes-Arriaga, Amin / Fahn, Stanley / Tolosa, Eduardo. ·Movement Disorders Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico, USA. · Department of Neurology, Columbia University Medical Center, New York, USA. · Neurological Tissue Bank, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid and Universidad de Barcelona, Barcelona, Spain. ·Rev Invest Clin · Pubmed #29265118.

ABSTRACT: An Essay on the Shaking Palsy, by James Parkinson, was published in 1817. Later, Jean-Martin Charcot better described some of the motor features of the disease and named the condition as "La Maladie de Parkinson." As understanding about the disease progressed, aided by both clinical expertise and technological developments, the definition of what is Parkinson's disease has evolved. Motor phenotype, non-motor symptoms, monogenic mutations, genetic risk factors, disease subtyping, and data-driven clusters, among other concepts, have given rise to the hypothesis that Parkinson's disease may be not one well-defined entity but several different diseases encompassed as a levodopa-responsive Parkinsonism. This review present and discusses several of these factors and how they may support or not the notion of Parkinson's being one or more diseases. In summary, current evidence appears to be insufficient at this moment to clarify this issue. Parkinson's disease will continue to be an evolving concept over the years to come.

11 Review Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's disease. 2017

Francardo, Veronica / Schmitz, Yvonne / Sulzer, David / Cenci, M Angela. ·Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: Veronica.Francardo@med.lu.se. · Departments Neurology, Psychiatry, Pharmacology, Columbia University Medical Center: Division of Molecular Therapeutics, New York State Psychiatric Institute, New York 10032, NY, USA. · Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: Angela.Cenci_Nilsson@med.lu.se. ·Exp Neurol · Pubmed #28988910.

ABSTRACT: Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial effects on multiple neural systems affected in PD. We further review past and current strategies to therapeutically stimulate these mediators, and discuss the preclinical evidence that exercise training can have neuroprotective and neurorestorative effects. A future translational task will be to combine behavioral and pharmacological interventions to exploit endogenous mechanisms of neuroprotection and neurorestoration for therapeutic purposes. This type of approach is likely to provide benefit to many PD patients, despite the clinical, etiological, and genetic heterogeneity of the disease.

12 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.

13 Review From Disease to Health: Physical Therapy Health Promotion Practices for Secondary Prevention in Adult and Pediatric Neurologic Populations. 2017

Quinn, Lori / Morgan, Don. ·Department of Biobehavioral Sciences, Teachers College, Columbia University, New York (L.Q.) · and Department of Health and Human Performance, Middle Tennessee State University, Murfreesboro (D.M.). ·J Neurol Phys Ther · Pubmed #28628596.

ABSTRACT: BACKGROUND AND PURPOSE: Over the last decade there has been a substantial increase in efforts to better understand how targeted physical activity and exercise interventions can be used to minimize secondary consequences arising from neurological damage in both adult and pediatric populations. This article offers an overview of contemporary research that addresses mediators of functional and neuroplastic adaptations associated with physical activity and exercise. We emphasize the important role that physical therapists can play to increase participation and improve well-being in adults and children with neurological disorders. We further highlight potential strategies to foster translation of evidence-based findings for use by clinicians and consumers. SUMMARY OF KEY POINTS: Engagement in physical activity can serve as a powerful promoter of health and well-being in adults and youth with neurologic disease, and has the potential to alter the course of disease processes. Physical therapists can play a key role in promoting fitness and wellness by encouraging active living, providing early diagnosis of disease and prescribing targeted activity interventions to improve fitness and participation, and helping individuals overcome personal and environmental barriers to an active lifestyle. RECOMMENDATIONS FOR CLINICAL PRACTICE: Physical therapists must adopt a model of rehabilitation that emphasizes secondary prevention in adults and youth with neurologic diseases. Physical therapists have a unique role in developing forward-thinking approaches in using innovative health and wellness strategies to promote positive changes in activity and exercise behaviors.

14 Review Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review. 2017

da Costa, Ianara Mendonça / Cavalcanti, José Rodolfo Lopes de Paiva / de Queiroz, Dinalva Brito / de Azevedo, Eduardo Pereira / do Rêgo, Amália Cinthia Meneses / Araújo Filho, Irami / Parente, Paulo / Botelho, Marco Antônio / Guzen, Fausto Pierdoná. ·Laboratory of Experimental Neurology, Department of Biomedical Sciences, Health Science Center, State University of Rio Grande do Norte, Mossoró, RN, Brazil. · Post Graduation Program in Biotechnology, Potiguar University (UnP) School of Health, Natal, RN, Brazil. · Neural Engineering and Control Lab. Dept. of Biomedical Engineering, Columbia University, New York, USA. ·Phytother Res · Pubmed #28544038.

ABSTRACT: Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti-apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.

15 Review Genetic Forms of Parkinson's Disease. 2017

Kim, Christine Y / Alcalay, Roy N. ·Department of Movement Disorders, Columbia University Medical Center, New York, New York. · Department of Neurology, Columbia University Medical Center, New York, New York. ·Semin Neurol · Pubmed #28511254.

ABSTRACT: One of the greatest advances in Parkinson's disease (PD) research in the past two decades has been a better understanding of PD genetics. Of the many candidate genes investigated, the best studied include

16 Review Clinical Features of LRRK2 Carriers with Parkinson's Disease. 2017

Kestenbaum, Meir / Alcalay, Roy N. ·Department of Neurology, Columbia University Medical Center, New York, NY, USA. · Department of Neurology, Columbia University Medical Center, New York, NY, USA. rna2104@columbia.edu. ·Adv Neurobiol · Pubmed #28353277.

ABSTRACT: LRRK2 mutations are present in 1% of all sporadic Parkinson's disease (PD) cases and 5% of all familial PD cases. Several mutations in the LRRK2 gene are associated with PD, the most common of which is the Gly2019Ser mutation. In the following review, we summarize the demographics and motor and non-motor symptoms of LRRK2 carriers with PD, as well as symptoms in non-manifesting carriers. The clinical features of LRRK2-associated PD are often indistinguishable from those of idiopathic PD on an individual basis. However, LRRK2 PD patients are likely to have less non-motor symptoms compared to idiopathic PD patients, including less olfactory and cognitive impairment. LRRK2-associated PD patients are less likely to report REM sleep behavior disorder (RBD) than noncarriers. In addition, it is possible that carriers are more prone to cancer than noncarriers with PD, but larger studies are required to confirm this observation. Development of more sensitive biomarkers to identify mutation carriers at risk of developing PD, as well as biomarkers of disease progression among LRRK2 carriers with PD, is required. Such biomarkers would help evaluate interventions, which may prevent PD among non-manifesting carriers, or slow down disease progression among carriers with PD.

17 Review The two-century journey of Parkinson disease research. 2017

Przedborski, Serge. ·Departments of Neurology, Pathology, and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. ·Nat Rev Neurosci · Pubmed #28303016.

ABSTRACT: Since the first formal description of Parkinson disease (PD) two centuries ago, our understanding of this common neurodegenerative disorder has expanded at all levels of description, from the delineation of its clinical phenotype to the identification of its neuropathological features, neurochemical processes and genetic factors. Along the way, findings have led to novel hypotheses about how the disease develops and progresses, challenging our understanding of how neurodegenerative disorders wreak havoc on human health. In this Timeline article, I recount the fascinating 200-year journey of PD research.

18 Review Convection-Enhanced Delivery. 2017

Mehta, A M / Sonabend, A M / Bruce, J N. ·Department of Neurological Surgery, Columbia University Medical Center, New York, NY, 10032, USA. · Department of Neurological Surgery, Columbia University Medical Center, New York, NY, 10032, USA. jnb2@cumc.columbia.edu. ·Neurotherapeutics · Pubmed #28299724.

ABSTRACT: Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood-brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to deliver a variety of therapeutic compounds for a diversity of diseases, including malignant gliomas, Parkinson's disease, and Alzheimer's disease. While a number of technological advances have been made since its development in the early 1990s, clinical trials with CED have been largely unsuccessful, and have illuminated a number of parameters that still need to be addressed for successful clinical application. This review addresses the physical principles behind CED, limitations in the technique, as well as means to overcome these limitations, clinical trials that have been performed, and future developments.

19 Review Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease. 2017

Zucca, Fabio A / Segura-Aguilar, Juan / Ferrari, Emanuele / Muñoz, Patricia / Paris, Irmgard / Sulzer, David / Sarna, Tadeusz / Casella, Luigi / Zecca, Luigi. ·Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy. · Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile. · Faculty of Medicine, Molecular and Clinical Pharmacology, ICBM, University of Chile, Santiago, Chile; Department of Basic Sciences, Faculty of Sciences, Santo Tomás University, Viña del Mar, Chile. · Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Department of Pharmacology, Columbia University Medical Center, New York, NY, USA. · Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. · Department of Chemistry, University of Pavia, Pavia, Italy. · Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy. Electronic address: luigi.zecca@itb.cnr.it. ·Prog Neurobiol · Pubmed #26455458.

ABSTRACT: There are several interrelated mechanisms involving iron, dopamine, and neuromelanin in neurons. Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal populations most targeted in Parkinson's disease. Many cellular redox reactions rely on iron, however an altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson's disease patients are present. Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like neuromelanin, and this process rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the neuromelanin-iron complex, since neuromelanin is an effective metal chelator. Neuromelanin serves to trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron, dopamine, and neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be disrupted. Indeed, when neuromelanin-containing organelles accumulate high load of toxins and iron during aging a neurodegenerative process can be triggered. In addition, neuromelanin released by degenerating neurons activates microglia and the latter cause neurons death with further release of neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration. Considering the above issues, age-related accumulation of neuromelanin in dopamine neurons shows an interesting link between aging and neurodegeneration.

20 Review Defects in trafficking bridge Parkinson's disease pathology and genetics. 2016

Abeliovich, Asa / Gitler, Aaron D. ·Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA. · Department of Neurology, Columbia University, New York, New York 10032, USA. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York 10032, USA. · Department of Genetics, Stanford University, Stanford, California 94305, USA. ·Nature · Pubmed #27830778.

ABSTRACT: Parkinson's disease is a debilitating, age-associated movement disorder. A central aspect of the pathophysiology of Parkinson's disease is the progressive demise of midbrain dopamine neurons and their axonal projections, but the underlying causes of this loss are unclear. Advances in genetics and experimental model systems have illuminated an important role for defects in intracellular transport pathways to lysosomes. The accumulation of altered proteins and damaged mitochondria, particularly at axon terminals, ultimately might overwhelm the capacity of intracellular disposal mechanisms. Cell-extrinsic mechanisms, including inflammation and prion-like spreading, are proposed to have both protective and deleterious functions in Parkinson's disease.

21 Review Is Axonal Degeneration a Key Early Event in Parkinson's Disease? 2016

Kurowska, Zuzanna / Kordower, Jeffrey H / Stoessl, A Jon / Burke, Robert E / Brundin, Patrik / Yue, Zhenyu / Brady, Scott T / Milbrandt, Jeffrey / Trapp, Bruce D / Sherer, Todd B / Medicetty, Satish. ·Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. · Renovo Neural Inc., Cleveland, OH, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, IL, USA. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, MI, USA. · Pacific Parkinson's Research Centre, Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia and Vancouver Coastal Health, BC, Canada. · Departments of Neurology and Pathology & Cell Biology, Columbia University Medical Center, New York City, NY, USA. · Departments of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA; Marine Biological Laboratory, Woods Hole, MA, USA. · Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. · The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA. ·J Parkinsons Dis · Pubmed #27497486.

ABSTRACT: Recent research suggests that in Parkinson's disease the long, thin and unmyelinated axons of dopaminergic neurons degenerate early in the disease process. We organized a workshop entitled 'Axonal Pathology in Parkinson's disease', on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing the state-of-the-art and defining key gaps in knowledge. A group of eight research leaders discussed new developments in clinical pathology, functional imaging, animal models, and mechanisms of degeneration including neuroinflammation, autophagy and axonal transport deficits. While the workshop focused on PD, comparisons were made to other neurological conditions where axonal degeneration is well recognized.

22 Review Levodopa therapy for Parkinson disease: A look backward and forward. 2016

LeWitt, Peter A / Fahn, Stanley. ·From the Department of Neurology (P.A.L.), Henry Ford Hospital · Department of Neurology (P.A.L.), Wayne State University School of Medicine, Detroit, MI · and Department of Neurology (S.F.), Columbia University Medical Center, New York, NY. ·Neurology · Pubmed #27044648.

ABSTRACT: Although levodopa is widely recognized as the most effective therapy for Parkinson disease (PD), its introduction 5 decades ago was preceded by several years of uncertainty and equivocal clinical results. The translation of basic neuroscience research by Arvid Carlsson and Oleh Hornykiewicz provided a logical pathway for treating PD with levodopa. Yet the pioneering clinicians who transformed PD therapeutics with this drug--among them Walther Birkmayer, Isamu Sano, Patrick McGeer, George Cotzias, Melvin Yahr, and others--faced many challenges in determining whether the concept and the method for replenishing deficient striatal dopamine was correct. This article reviews highlights in the early development of levodopa therapy. In addition, it provides an overview of emerging drug delivery strategies that show promise for improving levodopa's pharmacologic limitations.

23 Review Retrograde Axonal Degeneration in Parkinson Disease. 2016

Tagliaferro, Patricia / Burke, Robert E. ·Department of Neurology, Columbia University Medical Center, New York, NY, USA. · Departments of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA. ·J Parkinsons Dis · Pubmed #27003783.

ABSTRACT: In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson's disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics.

24 Review Comorbidity between neurological illness and psychiatric disorders. 2016

Hesdorffer, Dale C. ·Gertrude H. Sergievsky Center and Department of Epidemiology,Columbia University,New York,New York,USA. ·CNS Spectr · Pubmed #26898322.

ABSTRACT: Psychiatric disorders are common in many neurological disorders, including epilepsy, migraine, Alzheimer's disease, Parkinson's disease, essential tremor, and stroke. These comorbidities increase disease burden and may complicate the treatment of the combined disorders. Initial studies of the comorbidity of psychiatric and neurological disorders were cross-sectional, and time order of the associations was impossible to elucidate. More recent work has clarified time associations between psychiatric disorders and neurological disorders, particularly in epilepsy and stroke where epidemiological evidence suggests that there is a bidirectional relationship. This article takes an epidemiological approach to understanding these relationships and focuses mostly on epilepsy. Although, these relationships are understood in many neurological disorders, routine screening for psychiatric disorders in neurological disorders is infrequent, mostly due to the lack of partnerships between psychiatrists and neurologists and the paucity of neuropsychiatrists. Much more needs to be done to improve the detection and treatment of patients affected by neurological and psychiatric disorders. Understanding the scope of this overlap may inspire collaborations to improve the lives of people affected by both disorders.

25 Review Distress from Motivational Dis-integration: When Fundamental Motives Are Too Weak or Too Strong. 2016

Cornwell, James F M / Franks, Becca / Higgins, E Tory. ·Department of Behavioral Sciences and Leadership, United States Military Academy, 281 Thayer Hall, West Point, New York, NY, 10996, USA. jamesfcornwell@gmail.com. · Animal Welfare Program, University of British Columbia, 2357 Main Mall, Vancouver, BC, V6T 1Z4, Canada. · Department of Psychology, Columbia University, 406 Schermerhorn Hall, 1190 Amsterdam Ave. MC 5501, New York, NY, 10027, USA. ·Curr Top Behav Neurosci · Pubmed #26419241.

ABSTRACT: Past research has shown that satisfying different kinds of fundamental motives contributes to well-being. More recently, advances in motivational theory have shown that z is also tied to the integration of different motives. In other words, well-being depends not only on maximizing effectiveness in satisfying specific motives, but also on ensuring that motives work together such that no individual motive is too weak or too strong. In this chapter, we review existing research to show that specific forms of psychological distress can be linked to specific types of motivational imbalance or dis-integration. Such disintegration can arise from either excessive weakness of a specific motive or the excessive strength and/or dominance of a specific motive, thereby inhibiting other motives. Possible neural correlates and avenues of intervention are discussed.

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