August 15, 20112011; doi: 10.1101/cshperspect.a007500 originally published onlineCold Spring Harb Perspect Biol Daryl A. Bosco, Matthew J. LaVoie, Gregory A. Petsko and Dagmar Ringe Amyotrophic Lateral SclerosisProteostasis and Movement Disorders: Parkinson's Disease andSubject Collection Protein HomeostasisProtein Folding and Quality Control in the ERKazutaka Araki and Kazuhiro NagataProtein Folding and Quality Control in the ERKazutaka Araki and Kazuhiro NagataProtein Misfolding and Retinal DegenerationRadouil Tzekov, Linda Stein and Shalesh KaushalGeneric View of Protein Misfolding DisordersProtein Solubility and Protein Homeostasis: AChristopher M. DobsonMichele Vendruscolo, Tuomas P.J. Knowles andAggregation Diseases-Progress and PrognosisandProteostasis to Ameliorate Protein Misfolding Chemical and Biological Approaches for AdaptingSusan L. Lindquist and Jeffery W. KellySclerosisParkinson's Disease and Amyotrophic Lateral Proteostasis and Movement Disorders:Petsko, et al.Daryl A. Bosco, Matthew J. LaVoie, Gregory A.Mitochondria: Role in Cell Survival and DeathER Stress and Its Functional Link toJyoti D. Malhotra and Randal J. KaufmanQuality Control of Mitochondrial ProteostasisLangerMichael J. Baker, Takashi Tatsuta and ThomasAlzheimer's DiseaseDennis J. SelkoeCellular Strategies of Protein Quality ControlBryan Chen, Marco Retzlaff, Thomas Roos, et al.PrionsDavid W. Colby and Stanley B. PrusinerCells to Multicellular OrganismsThe Stress of Protein Misfolding: From SingleMorimotoTali Gidalevitz, Veena Prahlad and Richard I.Huntington's DiseaseSteven FinkbeinerAging as an Event of Proteostasis CollapseRebecca C. Taylor and Andrew DillinProkaryotesIntegrating Protein Homeostasis Strategies inAxel Mogk, Damon Huber and Bernd BukauTissue Damage in Gain-of-Function DisordersChronica1-Antitrypsin Deficiency: A Prototype for Hepatic Fibrosis and Carcinogenesis inDavid H. Perlmutter and Gary A. Silvermanhttp://cshperspectives.cshlp.org/cgi/collection/ For additional articles in this collection, see Copyright © 2011 Cold Spring Harbor Laboratory Press; all rights reservedLaboratory Press at BRANDEIS UNIV on August 14, 2012 - Published by Cold Spring Harborhttp://cshperspectives.cshlp.org/Downloaded fromProteostasis and Movement Disorders:Parkinson’s Disease and AmyotrophicLateral SclerosisDaryl A. Bosco1, Matthew J. LaVoie2, Gregory A. Petsko2,3, and Dagmar Ringe2,31Department of Neurology, University of Massachusetts Medical Center, Worcester, Massachusetts 016552Department of Neurology and Center for Neurologic Diseases, Harvard Medical School and Brigham &Women’s Hospital, Boston, Massachusetts 021153Department of Biochemistry and Rosenstiel Basic Medical Sciences Research Center, Brandeis University,Waltham, Massachusetts 02454Correspondence: [email protected]’s disease (PD) is a movement disorder that afflicts over one million in the U.S.;amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) is less prevalent but also has ahigh incidence. The two disorders sometimes present together, making a comparativestudy of interest. Both ALS and PD are neurodegenerative diseases, and are characterizedby the presence of intraneuronal inclusions; however, different classes of neurons areaffected and the primary protein in the inclusions differs between the diseases, and insome cases is different in distinct forms of the same disease. These observations mightsuggest that the more general approach of proteostasis pathway alteration would be a power-ful one in treating these disorders. Examining results from human genetics and studies inmodel organisms, as well as from biochemical and biophysical characterization of the pro-teins involved in both diseases, we find that most instances of PD can be considered as arisingfrom the misfolding, and self-association to a toxic species, of the small neuronal protein a-synuclein, and that proteostasis strategies are likely to be of value for this disorder. For ALS,the situation is much more complex and less clear-cut; the available data are most consistentwith a view that ALS may actually be a family of disorders, presenting similarly but arisingfrom distinct and nonoverlapping causes, including mislocalization of some properlyfolded proteins and derangement of RNA quality control pathways. Applying proteostasisapproaches to this disease may require rethinking or broadening the concept of what proteo-stasis means.INTRODUCTION: NEUROLOGICDISORDERS OF MOVEMENTMore than two million Americans arebelieved to suffer from some form of neu-rodegenerative movement disorder, the totalcost of which is estimated to exceed $10 billionannually. Because no society on earth is sparedthe effects of these crippling diseases, the figuresfor other countries are similar, adjusted forpopulation differences. The neurodegenerativeEditors: Richard I. Morimoto, Dennis Selkoe, and Jeff KellyAdditional Perspectives on Protein Homeostasis available at www.cshperspectives.orgCopyright # 2011 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a007500Cite this article as Cold Spring Harb Perspect Biol 2011;3:a0075001Laboratory Press at BRANDEIS UNIV on August 14, 2012 - Published by Cold Spring Harborhttp://cshperspectives.cshlp.org/Downloaded fromdiseases Parkinson’s disease (PD) and amyotro-phic lateral sclerosis (ALS or Lou Gehrig’s dis-ease) are the most important of the movementdisorders from a proteostasis perspective. ALSis often classified separately, as a motor neurondisease, but there are a number of reasons forconsidering them together, of which perhapsthe most important is that the two sometimespresent together, as in the Parkinsonism-de-mentia complex of Guam (Lytico-bodig). Thismovement dis order occurs among the Cha-morro populations of Guam and the MarianaIslands and is frequently accompanied by amotor neuron disease resembling ALS. Thecourse of the disease is rapid, with death typi-cally occurring within 5 years (Steele 2005).PD is the second most common neurode-generative disease after Alzheimer’s disease(AD); estimates of prevalence range to over onemillion in the U.S. Although ALS is consid-ered a so-called “orphan disease” because of itsrelatively low prevalence (around 30,000 casesin the United States), the annual incidence ofALS is actually closer to that of Parkinson’s: 6000 for ALS versus 60,000 for PD in theUnited States; the much lower prevalence ofALS is because of its rapid
View Full Document
Unlocking...