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Parkinson Disease: HELP
Articles from Tennessee
Based on 184 articles published since 2008

These are the 184 published articles about Parkinson Disease that originated from Tennessee during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Editorial Can lifestyle modification slow progression of Parkinson disease? 2017

Hedera, Peter / Davis, Thomas L. ·From the Department of Neurology, Vanderbilt University Medical Center, Nashville, TN. peter.hedera@vanderbilt.edu. · From the Department of Neurology, Vanderbilt University Medical Center, Nashville, TN. ·Neurology · Pubmed #28972193.

ABSTRACT: -- No abstract --

2 Editorial Can fall of blood pressure prevent falls in Parkinson disease? 2014

Hedera, Peter / Friedman, Joseph H. ·From the Department of Neurology (P.H.), Vanderbilt University, Nashville, TN · Movement Disorders Program (J.H.F.), Butler Hospital, Providence · and the Department of Neurology (J.H.F.), Alpert Medical School of Brown University, Providence, RI. ·Neurology · Pubmed #24682972.

ABSTRACT: -- No abstract --

3 Editorial Beyond here be dragons: SIBO in Parkinson's disease. 2013

Pfeiffer, Ronald. ·The University of Tennessee Health Science Center, Memphis, TN. ·Mov Disord · Pubmed #24167009.

ABSTRACT: -- No abstract --

4 Editorial Is α-synuclein rising to the surface as a diagnostic biomarker for Parkinson disease? 2013

Cheshire, William P / Pfeiffer, Ronald F. ·From the Department of Neurology (W.P.C.), Mayo Clinic, Jacksonville, FL · and Department of Neurology (R.F.P.), University of Tennessee Health Science Center, Memphis. ·Neurology · Pubmed #24089391.

ABSTRACT: In his historic manuscript on the "shaking palsy," James Parkinson expressed the hope "that some remedial process may ere long be discovered, by which, at least, the progress of the disease may be stopped."(1) Realization of that hope will require not only the discovery of a treatment that can halt or slow the progression of Parkinson disease (PD), but also the identification of early, accurate, and accessible biomarkers, for by the time the cardinal clinical signs of bradykinesia, rigidity, tremor, and postural instability appear, substantial destruction of nigrostriatal dopaminergic neurons has already occurred.

5 Review Degenerative or Debilitative Neurologic Syndromes. 2018

Parish, Abby Luck. ·Vanderbilt University School of Nursing, 461 21st Avenue South, Nashville, TN 37240, USA. Electronic address: abby.parish@vanderbilt.edu. ·Nurs Clin North Am · Pubmed #30100009.

ABSTRACT: Neurodegenerative disorders are progressive, debilitating impairments of neurologic function. Dementia affects cognition and function. Persons with cognitive deficits should undergo a full workup and may be treated with cholinesterase inhibitors and/or memantine. Behavioral and psychological symptoms of dementia may be assessed and treated individually. Parkinson disease is a disorder of movement. Levodopa is the standard treatment of dopamine-related movement symptoms. Associated symptoms should be assessed and treated. Other neurodegenerative syndromes are less common but highly debilitating. Currently, there are no curative or disease-modifying therapies for neurodegenerative disorders. Novel therapies or research are in the pipeline.

6 Review Positron emission tomography in Parkinson's disease: insights into impulsivity. 2017

Stark, Adam J / Claassen, Daniel O. ·a Department of Neurology , Vanderbilt University Medical Center , Nashville , TN , USA. ·Int Rev Psychiatry · Pubmed #29206483.

ABSTRACT: This study reviews previous studies that employ positron emission tomography (PET) imaging assessments in Parkinson's disease (PD) patients with and without Impulsive Compulsive Behaviours (ICB). This begins with a summary of the potential benefits and limitations of commonly utilized ligands, specifically D

7 Review Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease. 2017

Shibao, Cyndya A / Kaufmann, Horacio. ·Division of Clinical Pharmacology, Department of Medicine, Vanderbilt Autonomic Dysfunction Center, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Neurology, NYU Langone Medical Center, Dysautonomia Center, 530 1st Avenue, New York, NY, USA. horacio.kaufmann@nyumc.org. ·CNS Drugs · Pubmed #29076058.

ABSTRACT: Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.

8 Review Manganese and the Insulin-IGF Signaling Network in Huntington's Disease and Other Neurodegenerative Disorders. 2017

Bryan, Miles R / Bowman, Aaron B. ·Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. miles.r.bryan@vanderbilt.edu. · Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. miles.r.bryan@vanderbilt.edu. · Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. miles.r.bryan@vanderbilt.edu. · Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. · Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. · Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. · Vanderbilt Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. ·Adv Neurobiol · Pubmed #28889265.

ABSTRACT: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival. Manganese (Mn) is an essential metal to all biological systems but, in excess, can be toxic. Interestingly, several studies have revealed the insulin-mimetic effects of Mn-demonstrating Mn can activate several of the same metabolic kinases and increase peripheral and neuronal insulin and IGF-1 levels in rodent models. Separate studies have shown mouse and human striatal neuroprogenitor cell (NPC) models exhibit a deficit in cellular Mn uptake, indicative of a Mn deficiency. Furthermore, evidence from the literature reveals a striking overlap between cellular consequences of Mn deficiency (i.e., impaired function of Mn-dependent enzymes) and known HD endophenotypes including excitotoxicity, increased reactive oxygen species (ROS) accumulation, and decreased mitochondrial function. Here we review published evidence supporting a hypothesis that (1) the potent effect of IGF or insulin treatment on HD models, (2) the insulin-mimetic effects of Mn, and (3) the newly discovered Mn-dependent perturbations in HD may all be functionally related. Together, this review will present the intriguing possibility that intricate regulatory cross-talk exists between Mn biology and/or toxicology and the insulin/IGF signaling pathways which may be deeply connected to HD pathology and, perhaps, other neurodegenerative diseases (NDDs) and other neuropathological conditions.

9 Review Impulse Control and Related Disorders in Parkinson's Disease. 2017

Weintraub, Daniel / Claassen, Daniel O. ·Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Parkinson's Disease and Mental Illness Research, Education and Clinical Centers, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States. Electronic address: daniel.weintraub@uphs.upenn.edu. · Vanderbilt University School of Medicine, Nashville, TN, United States. ·Int Rev Neurobiol · Pubmed #28802938.

ABSTRACT: Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

10 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.

11 Review Impulse Control Disorders and Related Complications of Parkinson's Disease Therapy. 2017

Lopez, Alexander M / Weintraub, Daniel / Claassen, Daniel O. ·Department of Medicine, Meharry Medical College, Nashville, Tennessee. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. · Department of Neurology, Vanderbilt University, Nashville, Tennessee. ·Semin Neurol · Pubmed #28511259.

ABSTRACT: Impulsive and compulsive behaviors in Parkinson's disease (PD) patients are most often attributed to dopamine agonist therapy; dysregulation of the mesocorticolimbic system accounts for this behavioral phenotype. The clinical presentation is commonly termed

12 Review "Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies". 2016

Peres, Tanara V / Schettinger, Maria Rosa C / Chen, Pan / Carvalho, Fabiano / Avila, Daiana S / Bowman, Aaron B / Aschner, Michael. ·Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, 10461, NY, USA. tanara.peres-vieira@einstein.yu.edu. · Department of Biochemistry and Molecular Biology, CCNE, Federal University of Santa Maria, Camobi, Santa Maria, Brazil. · Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, 10461, NY, USA. · Laboratório do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa, Uruguaiana, RS, Brazil. · Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, 10461, NY, USA. michael.aschner@einstein.yu.edu. ·BMC Pharmacol Toxicol · Pubmed #27814772.

ABSTRACT: Manganese (Mn) is an essential heavy metal. However, Mn's nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication. We report that exposure to Mn may arise from environmental sources, occupational settings, food, total parenteral nutrition (TPN), methcathinone drug abuse or even genetic factors, such as mutation in the transporter SLC30A10. Accumulation of Mn occurs mainly in the basal ganglia and leads to a syndrome called manganism, whose symptoms of cognitive dysfunction and motor impairment resemble Parkinson's disease (PD). Various neurotransmitter systems may be impaired due to Mn, especially dopaminergic, but also cholinergic and GABAergic. Several proteins have been identified to transport Mn, including divalent metal tranporter-1 (DMT-1), SLC30A10, transferrin and ferroportin and allow its accumulation in the central nervous system. Parallel to identification of Mn neurotoxic properties, neuroprotective strategies have been reported, and these include endogenous antioxidants (for instance, vitamin E), plant extracts (complex mixtures containing polyphenols and non-characterized components), iron chelating agents, precursors of glutathione (GSH), and synthetic compounds that can experimentally afford protection against Mn-induced neurotoxicity.

13 Review Exercise and Nutritional Benefits in PD: Rodent Models and Clinical Settings. 2016

Archer, Trevor / Kostrzewa, Richard M. ·Department of Psychology, University of Gothenburg, Gothenburg, Sweden. trevor.archer@psy.gu.se. · Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37604, USA. ·Curr Top Behav Neurosci · Pubmed #26728168.

ABSTRACT: Physical exercise offers a highly effective health-endowering activity as has been evidence using rodent models of Parkinson's disease (PD). It is a particularly useful intervention in individuals employed in sedentary occupations or afflicted by a neurodegenerative disorder, such as PD. The several links between exercise and quality-of-life, disorder progression and staging, risk factors and symptoms-biomarkers in PD all endower a promise for improved prognosis. Nutrition provides a strong determinant for disorder vulnerability and prognosis with fish oils and vegetables with a mediterranean diet offering both protection and resistance. Three factors determining the effects of exercise on disorder severity of patients may be presented: (i) Exercise effects upon motor impairment, gait, posture and balance, (ii) Exercise reduction of oxidative stress, stimulation of mitochondrial biogenesis and up-regulation of autophagy, and (iii) Exercise stimulation of dopamine (DA) neurochemistry and trophic factors. Running-wheel performance, as measured by distance run by individual mice from different treatment groups, was related to DA-integrity, indexed by striatal DA levels. Finally, both nutrition and exercise may facilitate positive epigenetic outcomes, such as lowering the dosage of L-Dopa required for a therapeutic effect.

14 Review Cognitive Impairment in Fall-Related Studies in Parkinson's Disease. 2015

Domingos, Josefa M / Godinho, Catarina / Dean, John / Coelho, Miguel / Pinto, Anabela / Bloem, Bastiaan R / Ferreira, Joaquim J. ·CNS - Campus Neurológico Sénior, Torres Vedras, Portugal. · Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal. · Center for Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal. · Life Care Centers of America, Cleveland, Tennessee, USA. · Department of Rehabilitation, Hospital Santa Maria, Lisbon, Portugal. · Department of Neurology, University Medical Centre St Radboud, Nijmegen, The Netherlands. · Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal. ·J Parkinsons Dis · Pubmed #26406125.

ABSTRACT: BACKGROUND: There is increasing evidence to suggest a tight relationship between cognitive impairment and falls in Parkinson's disease (PD). Here, we draw attention to a potentially significant flaw in the existent falls-related research, namely the apparent exclusion of patients with cognitive impairment or dementia. OBJECTIVE: Our objective was to review all published, on-going or scheduled fall-related intervention studies, in order to investigate the extent to which cognitively impaired individuals with PD were included in these studies. METHODS: We analyzed published controlled trials regarding falls and PD in commonly used databases, as well as relevant ongoing clinical trials registered within the World Health Organization database, clinicaltrials.gov and the European Clinical Trials Database. RESULTS: Fourteen of the fifteen published studies included had explicit cognitive exclusion criteria as part of their study protocol. Most of the 54 on-going PD fall-related studies excluded patients with cognitive impairment. CONCLUSIONS: This suggests that individuals with cognitive impairment or dementia are excluded from fall-related research studies. We strongly recommend that future work in this area should include a representative sample of patients with PD, including subjects with cognitive decline.

15 Review Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease. 2015

Bastide, Matthieu F / Meissner, Wassilios G / Picconi, Barbara / Fasano, Stefania / Fernagut, Pierre-Olivier / Feyder, Michael / Francardo, Veronica / Alcacer, Cristina / Ding, Yunmin / Brambilla, Riccardo / Fisone, Gilberto / Jon Stoessl, A / Bourdenx, Mathieu / Engeln, Michel / Navailles, Sylvia / De Deurwaerdère, Philippe / Ko, Wai Kin D / Simola, Nicola / Morelli, Micaela / Groc, Laurent / Rodriguez, Maria-Cruz / Gurevich, Eugenia V / Quik, Maryka / Morari, Michele / Mellone, Manuela / Gardoni, Fabrizio / Tronci, Elisabetta / Guehl, Dominique / Tison, François / Crossman, Alan R / Kang, Un Jung / Steece-Collier, Kathy / Fox, Susan / Carta, Manolo / Angela Cenci, M / Bézard, Erwan. ·Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Department of Neurology, University Hospital Bordeaux, France. · Laboratory of Neurophysiology, Fondazione Santa Lucia, IRCCS, Rome, Italy. · Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy. · Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. · Department of Neurology, Columbia University, New York, USA. · Pacific Parkinson's Research Centre and National Parkinson Foundation Centre of Excellence, University of British Columbia, Vancouver, Canada. · Department of Biomedical Sciences, Section of Neuropsychopharmacology, Cagliari University, 09124 Cagliari, Italy. · Univ. de Bordeaux, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France; CNRS, Institut Interdisciplinaire de neurosciences, UMR 5297, 33000 Bordeaux, France. · Department of Neurology, Hospital Universitario Donostia and Neuroscience Unit, Bio Donostia Research Institute, San Sebastian, Spain. · Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · Center for Health Sciences, SRI International, CA 94025, USA. · Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy. · Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy. · Department of Biomedical Sciences, Physiology Section, Cagliari University, Cagliari, Italy. · Motac Neuroscience Ltd, Manchester, UK. · Michigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA. · Morton & Gloria Shulman Movement Disorders Center, Toronto Western Hospital, Toronto, Ontario M4T 2S8, Canada. · Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, UK. Electronic address: erwan.bezard@u-bordeaux.fr. ·Prog Neurobiol · Pubmed #26209473.

ABSTRACT: Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.

16 Review Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features. 2015

Kwakye, Gunnar F / Paoliello, Monica M B / Mukhopadhyay, Somshuvra / Bowman, Aaron B / Aschner, Michael. ·Neuroscience Department, Oberlin College, Oberlin, OH 44074, USA. gkwakye@oberlin.edu. · Graduate Program in Public Health, Department of Pathology, Clinical and Toxicological Analysis, Center of Health Science, State University of Londrina, Parana 10011, Brazil. monibas2@gmail.com. · Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular & Molecular Biology, and Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA. som@austin.utexas.edu. · Department of Neurology and Pediatrics, Vanderbilt University, Nashville, TN 37240, USA. aaron.bowman@vanderbilt.edu. · Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Michael.Aschner@einstein.yu.edu. ·Int J Environ Res Public Health · Pubmed #26154659.

ABSTRACT: Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson's disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for manganism and idiopathic Parkinson's disease (PD).

17 Review Manganese homeostasis in the nervous system. 2015

Chen, Pan / Chakraborty, Sudipta / Mukhopadhyay, Somshuvra / Lee, Eunsook / Paoliello, Monica M B / Bowman, Aaron B / Aschner, Michael. ·Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. · Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Division of Pharmacology & Toxicology, College of Pharmacy; Institute for Cellular & Molecular Biology; and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA. · Department of Physiology, Meharry Medical College, Nashville, Tennessee, USA. · Graduate Program in Public Health, Department of Pathology, Clinical and Toxicological Analysis, Center of Health Science, State University of Londrina, Parana, Brazil. · Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. ·J Neurochem · Pubmed #25982296.

ABSTRACT: Manganese (Mn) is an essential heavy metal that is naturally found in the environment. Daily intake through dietary sources provides the necessary amount required for several key physiological processes, including antioxidant defense, energy metabolism, immune function and others. However, overexposure from environmental sources can result in a condition known as manganism that features symptomatology similar to Parkinson's disease (PD). This disorder presents with debilitating motor and cognitive deficits that arise from a neurodegenerative process. In order to maintain a balance between its essentiality and neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels. These include transporters involved in Mn uptake, and newly discovered Mn efflux mechanisms. This review will focus on current studies related to mechanisms underlying Mn import and export, primarily the Mn transporters, and their function and roles in Mn-induced neurotoxicity. Though and essential metal, overexposure to manganese may result in neurodegenerative disease analogous to Parkinson's disease. Manganese homeostasis is tightly regulated by transporters, including transmembrane importers (divalent metal transporter 1, transferrin and its receptor, zinc transporters ZIP8 and Zip14, dopamine transporter, calcium channels, choline transporters and citrate transporters) and exporters (ferroportin and SLC30A10), as well as the intracellular trafficking proteins (SPCA1 and ATP12A2). A manganese-specific sensor, GPP130, has been identified, which affords means for monitoring intracellular levels of this metal.

18 Review Manganese Is Essential for Neuronal Health. 2015

Horning, Kyle J / Caito, Samuel W / Tipps, K Grace / Bowman, Aaron B / Aschner, Michael. ·Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232; email: kyle.j.horning@vanderbilt.edu , k.grace.tipps@vanderbilt.edu , aaron.bowman@vanderbilt.edu. ·Annu Rev Nutr · Pubmed #25974698.

ABSTRACT: The understanding of manganese (Mn) biology, in particular its cellular regulation and role in neurological disease, is an area of expanding interest. Mn is an essential micronutrient that is required for the activity of a diverse set of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary for life, Mn is toxic in excess. Thus, maintaining appropriate levels of intracellular Mn is critical. Unlike other essential metals, cell-level homeostatic mechanisms of Mn have not been identified. In this review, we discuss common forms of Mn exposure, absorption, and transport via regulated uptake/exchange at the gut and blood-brain barrier and via biliary excretion. We present the current understanding of cellular uptake and efflux as well as subcellular storage and transport of Mn. In addition, we highlight the Mn-dependent and Mn-responsive pathways implicated in the growing evidence of its role in Parkinson's disease and Huntington's disease. We conclude with suggestions for future focuses of Mn health-related research.

19 Review Role of the unfolded protein response in the pathogenesis of Parkinson's disease. 2015

Varma, Deeksha / Sen, Dwaipayan. ·Department of Genetic Engineering, SRM University, Chennai, TN, India; dwaipayan.sen@vit.ac.in. · School of Biosciences and Technology, Vellore Institute of Technology (VIT) University, Vellore, TN, India. ·Acta Neurobiol Exp (Wars) · Pubmed #25856519.

ABSTRACT: Parkinson's disease is the second most common neurodegenerative disease which affects almost 1 percent of the population above the age of 60. It is is characterized by loss of dopaminergic neurons in the striatum and substantia nigra, coupled with the formation of intracellular Lewy bodies in degenerating neurons. Recent evidence suggests endoplasmic reticulum stress as a common and prominent occurrence in the progression of Parkinson's disease pathogenesis in the affected human brain. One of the cellular defense mechanism to combat endoplasmic reticulum stress due to excessive protein accumulation is through activation of the unfolded protein response pathway. In this review we focus on the impact and role of this unfolded protein response as a causative factor of Parkinson's disease leading to neurodegeneration.

20 Review The link between Parkinson's disease and breast and prostate cancers: A meta-analysis. 2015

Wang, Tengfei. ·a Department of Pharmacology , University of Tennessee Health Science Center , Memphis , TN , USA. ·Int J Neurosci · Pubmed #25387067.

ABSTRACT: PURPOSE: Clinical observations have shown an increased morbidity for breast cancer or prostate cancer in patients with Parkinson's disease (PD), however, other reports have noted contradictory results. This pooled analysis was utilized to test whether PD is associated with the risk of breast or prostate cancer. METHODS: We searched PubMed, Embase and Cochrane library and conducted a meta-analysis to clarify the correlation of PD with breast and/or prostate cancer risk. We identified 16 eligible articles from which odds ratios with 95% confident intervals were assessed as main measures in the pooled estimation. Subgroup analyses and cumulative meta-analysis were also performed. RESULTS: Our results showed no PD risk associated with breast or prostate cancer in the overall population, which was supported by the results of cumulative meta-analyses. The subgroup analyses suggested no significant risk of breast or prostate cancer in patients with PD within relevant subsets, i.e. gender, ethnicity, PD diagnosis time or study design. No evidence of publication bias was observed across the involved studies. CONCLUSIONS: This meta-analysis indicates a lack of association between PD and risk of breast or prostate cancer.

21 Review Classics in chemical neuroscience: levodopa. 2014

Whitfield, A Connor / Moore, Ben T / Daniels, R Nathan. ·Department of Pharmaceutical Sciences, Lipscomb University College of Pharmacy and Health Sciences , Nashville, Tennessee 37204, United States. ·ACS Chem Neurosci · Pubmed #25270271.

ABSTRACT: Levodopa was the first and most successful breakthrough in the treatment of Parkinson's disease (PD). It is estimated that PD affects approximately 1 million people in the United States alone. Although PD was discovered in 1817, prior to levodopa's discovery there was not an effective treatment for managing its symptoms. In 1961, Hornykiewicz pioneered the use of levodopa to enhance dopamine levels in the striatum, significantly improving symptoms in many patients. With the addition of carbidopa in 1974, the frequency of gastrointestinal adverse drug reactions (ADRs) was significantly reduced, leading to the modern treatment of PD. Although levodopa treatment is more than 50 years old, it remains the "gold standard" for PD treatment. This Review describes in detail the synthesis, metabolism, pharmacology, ADRs, and importance of levodopa therapy to neuroscience in the past and present.

22 Review New targets for treating the underlying pathophysiology and nonmotor aspects of Parkinson's disease. 2014

Butler, Jonathan T / Tolleson, Christopher. ·Department of Neurology, Vanderbilt University, 1161 21st Avenue South, Medical Center North A- 0118, Nashville, Tennessee 37232, USA. jonathan.t.butler@vanderbilt.edu. ·CNS Neurol Disord Drug Targets · Pubmed #25230233.

ABSTRACT: Parkinson's disease is a common neurodegenerative disease diagnosed by well established clinical motor symptoms. However, the disease also encompasses many nonmotor issues that can impact a myriad of processes such as cardiovascular status, gastrointestinal function, autonomic function, mood and sleep. These issues can be more debilitating and impactful on health status in part because of a lack of effective treatments. The pathophysiology of the disease process is under active investigation with postulated mechanisms involving both the central nervous system and the periphery. More in depth examination of the many nonmotor symptoms may aid in the discovery of the overarching pathological origin and progression of Parkinson's disease. Examining the disease process from the perspective of nonmotor symptoms may also provide additional target pathways and potential drug development options not considered previously.

23 Review Creativity and neurological disease. 2014

Acosta, Lealani Mae Y. ·Department of Neurology, Vanderbilt University, 2525 West End Avenue, Suite 1200, Nashville, TN, 37203-8684, USA, lealani.mae.acosta@vanderbilt.edu. ·Curr Neurol Neurosci Rep · Pubmed #24938215.

ABSTRACT: Although humans have long valued creativity, the generation of such innovation is still incompletely understood. Looking at the healthy brain, researchers have localized certain parts for a basic understanding of these mechanisms. By researching the brain affected by neurological disease, scientists have observed unique manifestations of creativity, such as in frontotemporal lobar degeneration, Alzheimer's disease, Parkinson's disease and parkinsonian spectrum disorders, and stroke, which help clarify these creative underpinnings. Incorporating both healthy and disease models of cerebral functioning, neurological and neuroscientific research from recent years has built on established theories and expanded current knowledge.

24 Review Oxidative stress mechanisms underlying Parkinson's disease-associated neurodegeneration in C. elegans. 2013

Chakraborty, Sudipta / Bornhorst, Julia / Nguyen, Thuy T / Aschner, Michael. ·Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, TN 37232, USA. michael.aschner@einstein.yu.edu. ·Int J Mol Sci · Pubmed #24284401.

ABSTRACT: Oxidative stress is thought to play a significant role in the development and progression of neurodegenerative diseases. Although it is currently considered a hallmark of such processes, the interweaving of a multitude of signaling cascades hinders complete understanding of the direct role of oxidative stress in neurodegeneration. In addition to its extensive use as an aging model, some researchers have turned to the invertebrate model Caenorhabditis elegans (C. elegans) in order to further investigate molecular mediators that either exacerbate or protect against reactive oxygen species (ROS)-mediated neurodegeneration. Due to their fully characterized genome and short life cycle, rapid generation of C. elegans genetic models can be useful to study upstream markers of oxidative stress within interconnected signaling pathways. This report will focus on the roles of C. elegans homologs for the oxidative stress-associated transcription factor Nrf2, as well as the autosomal recessive, early-onset Parkinson's disease (PD)-associated proteins Parkin, DJ-1, and PINK1, in neurodegenerative processes.

25 Review Glutathione metabolism and Parkinson's disease. 2013

Smeyne, Michelle / Smeyne, Richard Jay. ·Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. · Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: Richard.smeyne@stjude.org. ·Free Radic Biol Med · Pubmed #23665395.

ABSTRACT: It has been established that oxidative stress, defined as the condition in which the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson disease. Glutathione is a ubiquitous thiol tripeptide that acts alone or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals, and peroxynitrites. In this review, we examine the synthesis, metabolism, and functional interactions of glutathione and discuss how these relate to the protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson disease.