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Parkinson Disease: HELP
Articles from NewYork-Presbyterian Hospitals
Based on 224 articles published since 2008
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These are the 224 published articles about Parkinson Disease that originated from NewYork-Presbyterian Hospitals during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9
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 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.

8 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.

9 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.

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 Management of Spinal Conditions in Patients With Parkinson Disease. 2017

Baker, Joseph F / McClelland, Shearwood / Hart, Robert A / Bess, R Shay. ·From the Department of Orthopaedic Surgery, Waikato Hospital, Hamilton, New Zealand (Dr. Baker), NYU Hospital for Joint Diseases, New York, NY (Dr. McClelland), the Department of Orthopaedic Surgery, Oregon Health and Science University, Portland, OR (Dr. Hart), and the Department of Orthopaedic Surgery, Presbyterian/St. Luke's Medical Center, Denver, CO (Dr. Bess). ·J Am Acad Orthop Surg · Pubmed #28692583.

ABSTRACT: Parkinson disease (PD) is increasingly prevalent in the aging population. Spine disorders in patients with PD may be degenerative in nature or may arise secondary to motor effects related to the parkinsonian disease process. Physicians providing care for patients with PD and spine pathologies must be aware of several factors that affect treatment, including the patterns of spinal deformity, complex drug interactions, and PD-associated osteoporosis. Following spine surgery, complication rates are higher in patients with PD than in those without the disease. Literature on spine surgery in this patient population is limited by small cohort size, the heterogeneous patient population, and variable treatment protocols. However, most studies emphasize the need for preoperative optimization of motor control with appropriate medications and deep brain stimulation, as well as consultation with a movement disorder specialist. Future studies must control for confounding variables, such as the type of surgery and PD severity, to improve understanding of spinal pathology and treatment options in this patient population.

14 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

15 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.

16 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.

17 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.

18 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.

19 Review Mitochondrial dysfunction in Parkinson's disease. 2016

Bose, Anindita / Beal, M Flint. ·Appel Alzheimer's Disease Research Institute, Brain and Mind Research Institute, Weill Cornell Medicine, New York City, New York, USA. anb2055@med.cornell.edu. · Brain and Mind Research Institute, Weill Cornell Medicine, New York City, New York, USA. fbeal@med.cornell.edu. ·J Neurochem · Pubmed #27546335.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disease. About 2% of the population above the age of 60 is affected by the disease. The pathological hallmarks of the disease include the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies that are made of α-synuclein. Several theories have been suggested for the pathogenesis of PD, of which mitochondrial dysfunction plays a pivotal role in both sporadic and familial forms of the disease. Dysfunction of the mitochondria that is caused by bioenergetic defects, mutations in mitochondrial DNA, nuclear DNA gene mutations linked to mitochondria, and changes in dynamics of the mitochondria such fusion or fission, changes in size and morphology, alterations in trafficking or transport, altered movement of mitochondria, impairment of transcription, and the presence of mutated proteins associated with mitochondria are implicated in PD. In this review, we provide a detailed overview of the mechanisms that can cause mitochondrial dysfunction in PD. We bring to the forefront, new signaling pathways such as the retromer-trafficking pathway and its implication in the disease and also provide a brief overview of therapeutic strategies to improve mitochondrial defects in PD. Bioenergetic defects, mutations in mitochondrial DNA, nuclear DNA gene mutations, alterations in mitochondrial dynamics, alterations in trafficking/transport and mitochondrial movement, abnormal size and morphology, impairment of transcription and the presence of mutated proteins associated with mitochondria are implicated in PD. In this review, we focus on the mechanisms underlying mitochondrial dysfunction in PD and bring to the forefront new signaling pathways that may be involved in PD. We also provide an overview of therapeutic strategies to improve mitochondrial defects in PD. This article is part of a special issue on Parkinson disease.

20 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.

21 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.

22 Review Microbiota-gut-brain signalling in Parkinson's disease: Implications for non-motor symptoms. 2016

Felice, Valeria D / Quigley, Eamonn M / Sullivan, Aideen M / O'Keeffe, Gerard W / O'Mahony, Siobhain M. ·Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland. · APC Microbiome Institute, University College Cork, Cork, Ireland; Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, and Weill Cornell Medical College, 6550 Fannin St, SM 1001, Houston, TX 77030, USA. · Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. · Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland. Electronic address: http://publish.ucc.ie/researchprofiles/C003/somahony. ·Parkinsonism Relat Disord · Pubmed #27013171.

ABSTRACT: Parkinson's disease is the second most common neurodegenerative disorder, affecting 1-2% of the population over 65 years of age. The primary neuropathology is the loss of midbrain dopaminergic neurons, resulting in characteristic motor deficits, upon which the clinical diagnosis is based. However, a number of significant non-motor symptoms (NMS) are also evident that appear to have a greater impact on the quality of life of these patients. In recent years, it has become increasingly apparent that neurobiological processes can be modified by the bi-directional communication that occurs along the brain-gut axis. The microbiota plays a key role in this communication throughout different routes in both physiological and pathological conditions. Thus, there has been an increasing interest in investigating how microbiota changes within the gastrointestinal tract may be implicated in health and disease including PD. Interestingly α-synuclein-aggregates, the cardinal neuropathological feature in PD, are present in both the submucosal and myenteric plexuses of the enteric nervous system, prior to their appearance in the brain, indicating a possible gut to brain route of "prion-like" spread. In this review we highlight the potential importance of gut to brain signalling in PD with particular focus on the role of the microbiota as major player in this communication.

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 Prostaglandin J2: a potential target for halting inflammation-induced neurodegeneration. 2016

Figueiredo-Pereira, Maria E / Corwin, Chuhyon / Babich, John. ·Department of Biological Sciences, Hunter College and the Graduate Center, CUNY, New York, New York. · Department of Radiology, Weill Cornell Medical College, New York, New York. ·Ann N Y Acad Sci · Pubmed #26748744.

ABSTRACT: Prostaglandins (PGs) are produced via cyclooxygenases, which are enzymes that play a major role in neuroinflammation. Epidemiological studies show that chronic treatment with low levels of cyclooxygenase inhibitors (nonsteroidal anti-inflammatory drugs (NSAIDs)) lowers the risk for Alzheimer's disease (AD) and Parkinson's disease (PD) by as much as 50%. Unfortunately, inhibiting cyclooxygenases with NSAIDs blocks the synthesis of downstream neuroprotective and neurotoxic PGs, thus producing adverse side effects. We focus on prostaglandin J2 (PGJ2) because it is highly neurotoxic compared to PGA1, D2, and E2. Unlike other PGs, PGJ2 and its metabolites have a cyclopentenone ring with reactive α,β-unsaturated carbonyl groups that form covalent Michael adducts with key cysteines in proteins and GSH. Cysteine-binding electrophiles such as PGJ2 are considered to play an important role in determining whether neurons will live or die. We discuss in vitro and in vivo studies showing that PGJ2 induces pathological processes relevant to neurodegenerative disorders such as AD and PD. Further, we discuss our work showing that increasing intracellular cAMP with the lipophilic peptide PACAP27 counteracts some of the PGJ2-induced detrimental effects. New therapeutic strategies that neutralize the effects of specific neurotoxic PGs downstream from cyclooxygenases could have a significant impact on the treatment of chronic neurodegenerative disorders with fewer adverse side effects.

25 Review Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson's Disease. 2015

Robakis, Daphne / Fahn, Stanley. ·Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. ·CNS Drugs · Pubmed #26164425.

ABSTRACT: Inhibitors of monoamine oxidase-B (MAO-B) occupy an important place in the treatment of Parkinson's disease. Selegiline was the first MAO-B to be used therapeutically, while rasagiline is a second-generation drug with higher potency and selectivity. Safinamide is an investigational MAO-B inhibitor with non-dopaminergic properties that may provide advantages over its predecessors. As a class, MAO-B inhibitors are safe and well tolerated and provide symptomatic benefit both as monotherapy and in combination with other antiparkinsonian medications from early to late stages of disease. In combination with levodopa, MAO-B inhibitors may improve motor fluctuations and allow for lower total doses of levodopa. Patient characteristics and preferences can be important factors in deciding between agents. As a class, MAO-B inhibitors have shown promise as disease-modifying agents, but the clinical trial evidence to date has not been strong enough to afford them such a label. Future research may help further elucidate their relative merits and clarify their role in altering disease progression.

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